International Journal of Molecular Sciences

Editorial

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2 pages, 137 KiB

Open AccessEditorial

Dysregulation of Regulatory ncRNAs and Diseases

by Mohamed Raafat El-Gewely

Int. J. Mol. Sci. 2024, 25(1), 24; https://doi.org/10.3390/ijms25010024 - 19 Dec 2023

Cited by 14 | Viewed by 852

Abstract

Cancer was initially attributed to genetic mutations and gene alterations, which resemble genetic diseases caused by various modifications of a specific gene in the genome sequence [...] Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

Research

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17 pages, 1409 KiB

Open AccessArticle

Differential Expression of MicroRNA MiR-145 and MiR-155 Downstream Targets in Oral Cancers Exhibiting Limited Chemotherapy Resistance

by Conner Belnap, Tyler Divis, Karl Kingsley and Katherine M. Howard

Int. J. Mol. Sci. 2024, 25(4), 2167; https://doi.org/10.3390/ijms25042167 - 10 Feb 2024

Cited by 3 | Viewed by 1620

Abstract

New evidence has suggested that non-coding microRNAs play a significant role in mediating and modulating chemotherapy resistance, particularly among oral cancers. One recent study found that the upregulation of miR-145 and the downregulation of miR-155 strongly correlated with a limited chemotherapy resistance to [...] Read more.

New evidence has suggested that non-coding microRNAs play a significant role in mediating and modulating chemotherapy resistance, particularly among oral cancers. One recent study found that the upregulation of miR-145 and the downregulation of miR-155 strongly correlated with a limited chemotherapy resistance to Cisplatin, 5-Fluorouracil, and Paclitaxel, although the mechanism(s) responsible for these observations remain unidentified. Using commercially available cell lines of oral squamous cell carcinoma, RNA was isolated, converted into cDNA, and subsequently screened for the expression of downstream targets of miR-145 and miR-155 using qPCR. These results demonstrated the upregulation of miR-21, miR-125, miR-133, miR-365, miR-720, and miR-1246, as well as the downregulation of miR-140, miR-152, miR-218, miR-221, and miR-224. This screening also confirmed the differential expression and regulation of mir-145 and miR-155 among the cell lines with limited chemotherapy resistance (SCC15). In addition, several downstream targets of these specific microRNAs were upregulated by all oral cancer cell lines, such as MBTD1 and FSCN1, or downregulated in all cell lines, such as CLCN3, FLI-1, MRTFB, DAB, SRGAP1, and ABHD17C. However, three miR-145 downstream targets were identified in the least chemotherapy-resistant cells, exhibiting the differential upregulation of KCNA4 and SRGAP2, as well as the downregulation of FAM135A, with this expression pattern not detected in any of the other oral cancer cell lines. These data strongly support that the differential regulation of these three downstream targets may be related to the chemosensitivity of this oral cancer cell line. The potential involvement of these targets must be further investigated to determine how and whether mechanisms of these cellular pathways may be involved in the observed lack of chemotherapy resistance. These data may be important to design targets or treatments to reduce chemotherapy resistance and improve patient treatment outcomes. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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20 pages, 1264 KiB

Open AccessArticle

Long Non-Coding RNAs: Bridging Cancer-Associated Thrombosis and Clinical Outcome of Ovarian Cancer Patients

by Inês Soares Marques, Valéria Tavares, Joana Savva-Bordalo, Mariana Rei, Joana Liz-Pimenta, Inês Guerra de Melo, Joana Assis, Deolinda Pereira and Rui Medeiros

Int. J. Mol. Sci. 2024, 25(1), 140; https://doi.org/10.3390/ijms25010140 - 21 Dec 2023

Cited by 2 | Viewed by 1547

Abstract

Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic [...] Read more.

Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann–Whitney U test, p = 0.037; Χ² test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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16 pages, 5926 KiB

Open AccessArticle

Characterization of a miRNA Signature with Enhanced Diagnostic and Prognostic Power for Patients with Bladder Carcinoma

by Maria Samara, Panagiotis J. Vlachostergios, Eleni Thodou, Ioannis Zachos, Lampros Mitrakas, Konstantinos Evmorfopoulos, Vassilios Tzortzis and Antonis Giakountis

Int. J. Mol. Sci. 2023, 24(22), 16243; https://doi.org/10.3390/ijms242216243 - 13 Nov 2023

Cited by 2 | Viewed by 1320

Abstract

Bladder carcinoma is globally among the most prevalent cancers and is associated with a high mortality rate at advanced stages. Its detection relies on invasive diagnostic methods that are unpleasant for the patient. Non-invasive molecular biomarkers, such as miRNAs, could serve as alternatives [...] Read more.

Bladder carcinoma is globally among the most prevalent cancers and is associated with a high mortality rate at advanced stages. Its detection relies on invasive diagnostic methods that are unpleasant for the patient. Non-invasive molecular biomarkers, such as miRNAs, could serve as alternatives for early detection and prognosis of this malignancy. We designed a computational approach that combines transcriptome profiling, survival analyses, and calculation of diagnostic power in order to isolate miRNA signatures with high diagnostic and prognostic utility. Our analysis of TCGA-BLCA data from 429 patients yielded one miRNA signature, consisting of five upregulated and three downregulated miRNAs with cumulative diagnostic power that outperforms current diagnostic methods. The same miRNAs have a strong prognostic significance since their expression is associated with the overall survival of bladder cancer patients. We evaluated the expression of this signature in 19 solid cancer types, supporting its unique diagnostic utility for bladder carcinoma. We provide computational evidence regarding the functional implications of this miRNA signature in cell cycle regulation, demonstrating its abundance in body fluids, including peripheral blood and urine. Our study characterized a novel miRNA signature with the potential to serve as a non-invasive method for bladder cancer diagnosis and prognosis. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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14 pages, 1066 KiB

Open AccessArticle

3′IsomiR Species Composition Affects Reliable Quantification of miRNA/isomiR Variants by Poly(A) RT-qPCR: Impact on Small RNA-Seq Profiling Validation

by Adriana Ferre, Lucía Santiago, José Francisco Sánchez-Herrero, Olga López-Rodrigo, Josvany Sánchez-Curbelo, Lauro Sumoy, Lluís Bassas and Sara Larriba

Int. J. Mol. Sci. 2023, 24(20), 15436; https://doi.org/10.3390/ijms242015436 - 21 Oct 2023

Cited by 2 | Viewed by 1983

Abstract

Small RNA-sequencing (small RNA-seq) has revealed the presence of small RNA-naturally occurring variants such as microRNA (miRNA) isoforms or isomiRs. Due to their small size and the sequence similarity among miRNA isoforms, their validation by RT-qPCR is challenging. We previously identified two miR-31-5p [...] Read more.

Small RNA-sequencing (small RNA-seq) has revealed the presence of small RNA-naturally occurring variants such as microRNA (miRNA) isoforms or isomiRs. Due to their small size and the sequence similarity among miRNA isoforms, their validation by RT-qPCR is challenging. We previously identified two miR-31-5p isomiRs—the canonical and a 3′isomiR variant (3′ G addition)—which were differentially expressed between individuals with azoospermia of different origin. Here, we sought to determine the discriminatory capacity between these two closely-related miRNA isoforms of three alternative poly(A) based-RT-qPCR strategies in both synthetic and real biological context. We found that these poly(A) RT-qPCR strategies exhibit a significant cross-reactivity between these miR-31-5p isomiRs which differ by a single nucleotide, compromising the reliable quantification of individual miRNA isoforms. Fortunately, in the biological context, given that the two miRNA variants show changes in the same direction, RT-qPCR results were consistent with the findings of small RNA-seq study. We suggest that miRNA selection for RT-qPCR validation should be performed with care, prioritizing those canonical miRNAs that, in small RNA-seq, show parallel/homogeneous expression behavior with their most prevalent isomiRs, to avoid confounding RT-qPCR-based results. This is suggested as the current best strategy for robust biomarker selection to develop clinically useful tests. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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12 pages, 1062 KiB

Open AccessArticle

Impact of Mir196a-2 Genotypes on Colorectal Cancer Risk in Taiwan

by Te-Cheng Yueh, Yun-Chi Wang, Yu-Ting Chin, Yi-Chih Hung, Mei-Chin Mong, Ya-Chen Yang, Jen-Sheng Pei, Jian Gu, Chia-Wen Tsai, Da-Tian Bau and Wen-Shin Chang

Int. J. Mol. Sci. 2023, 24(14), 11613; https://doi.org/10.3390/ijms241411613 - 18 Jul 2023

Cited by 7 | Viewed by 1460

Abstract

We aimed to investigate the association between genotypes for mir146a and mir196a-2 and the risk of developing colorectal cancer (CRC). We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the mir146a rs2910164 and mir196a-2 rs11614913 genotypes in 362 CRC patients and [...] Read more.

We aimed to investigate the association between genotypes for mir146a and mir196a-2 and the risk of developing colorectal cancer (CRC). We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the mir146a rs2910164 and mir196a-2 rs11614913 genotypes in 362 CRC patients and 362 controls. We also assessed the interactions between these genotypes and age, gender, smoking, alcohol consumption, and BMI status on CRC risk. Additionally, the serum expression level of mir196a-2 was quantified using quantitative reverse transcription-PCR. Our findings demonstrated that among the controls, the proportions of TT, CT, and CC genotypes of mir196a-2 rs11614913 were 32.3%, 48.1%, and 19.6%, respectively. As for the cases, the proportions were 24.6%, 45.0%, and 30.4%, respectively. Logistic regression analysis revealed that the CC genotype carriers had a 2.04-fold increased risk (95% confidence interval [CI] = 1.36–3.06, p = 0.0008). Furthermore, carriers of the CT + CC genotypes also exhibited a significant association with CRC risk (odds ratio [OR] = 1.46, 95% CI = 1.06–2.03, p = 0.0261). Moreover, carriers of the CC genotype had significantly higher serum levels of mir196a-2 compared to those with the TT genotype (p < 0.0001), indicating a genotype-phenotype correlation. No association was found regarding mir146a rs2910164. In conclusion, mir196a-2 rs2910164 genotypes, along with their associated expression, can serve as predictive markers for CRC risk. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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35 pages, 5672 KiB

Open AccessArticle

Identification of lncRNAs Deregulated in Epithelial Ovarian Cancer Based on a Gene Expression Profiling Meta-Analysis

by Martín Salamini-Montemurri, Mónica Lamas-Maceiras, Lidia Lorenzo-Catoira, Ángel Vizoso-Vázquez, Aida Barreiro-Alonso, Esther Rodríguez-Belmonte, María Quindós-Varela and M. Esperanza Cerdán

Int. J. Mol. Sci. 2023, 24(13), 10798; https://doi.org/10.3390/ijms241310798 - 28 Jun 2023

Cited by 2 | Viewed by 3127

Abstract

Epithelial ovarian cancer (EOC) is one of the deadliest gynecological cancers worldwide, mainly because of its initially asymptomatic nature and consequently late diagnosis. Long non-coding RNAs (lncRNA) are non-coding transcripts of more than 200 nucleotides, whose deregulation is involved in pathologies such as [...] Read more.

Epithelial ovarian cancer (EOC) is one of the deadliest gynecological cancers worldwide, mainly because of its initially asymptomatic nature and consequently late diagnosis. Long non-coding RNAs (lncRNA) are non-coding transcripts of more than 200 nucleotides, whose deregulation is involved in pathologies such as EOC, and are therefore envisaged as future biomarkers. We present a meta-analysis of available gene expression profiling (microarray and RNA sequencing) studies from EOC patients to identify lncRNA genes with diagnostic and prognostic value. In this meta-analysis, we include 46 independent cohorts, along with available expression profiling data from EOC cell lines. Differential expression analyses were conducted to identify those lncRNAs that are deregulated in (i) EOC versus healthy ovary tissue, (ii) unfavorable versus more favorable prognosis, (iii) metastatic versus primary tumors, (iv) chemoresistant versus chemosensitive EOC, and (v) correlation to specific histological subtypes of EOC. From the results of this meta-analysis, we established a panel of lncRNAs that are highly correlated with EOC. The panel includes several lncRNAs that are already known and even functionally characterized in EOC, but also lncRNAs that have not been previously correlated with this cancer, and which are discussed in relation to their putative role in EOC and their potential use as clinically relevant tools. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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13 pages, 2302 KiB

Open AccessArticle

MiR-182-5p Is Upregulated in Hepatic Tissues from a Diet-Induced NAFLD/NASH/HCC C57BL/6J Mouse Model and Modulates Cyld and Foxo1 Expression

by Chiara Compagnoni, Roberta Capelli, Veronica Zelli, Alessandra Corrente, Davide Vecchiotti, Irene Flati, Mauro Di Vito Nolfi, Adriano Angelucci, Edoardo Alesse, Francesca Zazzeroni and Alessandra Tessitore

Int. J. Mol. Sci. 2023, 24(11), 9239; https://doi.org/10.3390/ijms24119239 - 25 May 2023

Cited by 5 | Viewed by 2077

Abstract

Non-alcoholic fatty liver disease (NAFLD) is considered a relevant liver chronic disease. Variable percentages of NAFLD cases progress from steatosis to steatohepatitis (NASH), cirrhosis and, eventually, hepatocellular carcinoma (HCC). In this study, we aimed to deepen our understanding of expression levels and functional [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is considered a relevant liver chronic disease. Variable percentages of NAFLD cases progress from steatosis to steatohepatitis (NASH), cirrhosis and, eventually, hepatocellular carcinoma (HCC). In this study, we aimed to deepen our understanding of expression levels and functional relationships between miR-182-5p and Cyld-Foxo1 in hepatic tissues from C57BL/6J mouse models of diet-induced NAFL/NASH/HCC progression. A miR-182-5p increase was detected early in livers as NAFLD damage progressed, and in tumors compared to peritumor normal tissues. An in vitro assay on HepG2 cells confirmed Cyld and Foxo1, both tumor-suppressor, as miR-182-5p target genes. According to miR-182-5p expression, decreased protein levels were observed in tumors compared to peritumor tissues. Analysis of miR-182-5p, Cyld and Foxo1 expression levels, based on datasets from human HCC samples, showed results consistent with those from our mouse models, and also highlighted the ability of miR-182-5p to distinguish between normal and tumor tissues (AUC 0.83). Overall, this study shows, for the first time, miR-182-5p overexpression and Cyld-Foxo1 downregulation in hepatic tissues and tumors from a diet-induced NAFLD/HCC mouse model. These data were confirmed by the analysis of datasets from human HCC samples, highlighting miR-182-5p diagnostic accuracy and demonstrating the need for further studies to assess its potential role as a biomarker or therapeutic target. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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18 pages, 2483 KiB

Open AccessArticle

Determination of Common microRNA Biomarker Candidates in Stage IV Melanoma Patients and a Human Melanoma Cell Line: A Potential Anti-Melanoma Agent Screening Model

by Elena Antonova, Anastasia Hambikova, Denis Shcherbakov, Vitaly Sukhov, Sonya Vysochanskaya, Inna Fadeeva, Denis Gorshenin, Ekaterina Sidorova, Maria Kashutina, Alina Zhdanova, Oleg Mitrokhin, Nadezhda Avvakumova and Yury Zhernov

Int. J. Mol. Sci. 2023, 24(11), 9160; https://doi.org/10.3390/ijms24119160 - 23 May 2023

Cited by 1 | Viewed by 2208

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that play an important role in regulating gene expression. Dysregulation of miRNA expression is commonly observed in cancer, and it can contribute to malignant cell growth. Melanoma is the most fatal type of skin malignant neoplasia. Some [...] Read more.

MicroRNAs (miRNAs) are small, non-coding RNAs that play an important role in regulating gene expression. Dysregulation of miRNA expression is commonly observed in cancer, and it can contribute to malignant cell growth. Melanoma is the most fatal type of skin malignant neoplasia. Some microRNAs can be prospective biomarkers for melanoma in stage IV (advanced) at higher risk of relapses and require validation for diagnostic purposes. This work aimed to (1) determine the most significant microRNA biomarker candidates in melanoma using content analysis of the scientific literature, (2) to show microRNA biomarker candidates’ diagnostic efficacy between melanoma patients and healthy control groups in a small-scale preliminary study by blood plasma PCR analysis, (3) to determine significant microRNA markers of the MelCher human melanoma cell line, which are also detected in patients with melanoma, that can be used as markers of drug anti-melanoma activity, and (4) test anti-melanoma activity of humic substances and chitosan by their ability to reduce level of marker microRNAs. The content analysis of the scientific literature showed that hsa-miR-149-3p, hsa-miR-150-5p, hsa-miR-193a-3p, hsa-miR-21-5p, and hsa-miR-155-5p are promising microRNA biomarker candidates for diagnosing melanoma. Estimating microRNA in plasma samples showed that hsa-miR-150-5p and hsa-miR-155-5p may have a diagnostic value for melanoma in stage IV (advanced). When comparing ΔCt hsa-miR-150-5p and ΔCt hsa-miR-155-5p levels in melanoma patients and healthy donors, statistically significant differences were found (p = 0.001 and p = 0.001 respectively). Rates ΔCt were significantly higher among melanoma patients (medians concerning the reference gene miR-320a were 1.63 (1.435; 2.975) and 6.345 (4.45; 6.98), respectively). Therefore, they persist only in plasma from the melanoma patients group but not in the healthy donors group. In human wild-type stage IV melanoma (MelCher) cell culture, the presence of hsa-miR-150-5p and hsa-miR-155-5p in supernatant was detected. The ability of humic substance fractions and chitosan to reduce levels of hsa-miR-150-5p and hsa-miR-155-5p was tested on MelCher cultures, which is associated with anti-melanoma activity. It was found that the hymatomelanic acid (HMA) fraction and its subfraction UPLC-HMA statistically significantly reduced the expression of miR-150-5p and miR-155-5p (p ≤ 0.05). For the humic acid (HA) fraction, this activity was determined only to reduce miR-155-5p (p ≤ 0.05). Ability to reduce miR-150-5p and miR-155-5p expression on MelCher cultures was not determined for chitosan fractions with a molecular weight of 10 kDa, 120 kDa, or 500 kDa. Anti-melanoma activity was also determined in the MTT test on MelCher cultures for explored substances. The median toxic concentration (TC50) was determined for HA, HMA and UPLC-HMA (39.3, 39.7 and 52.0 μg/mL, respectively). For 10 kDa, 120 kDa, or 500 kDa chitosan fractions TC50 was much higher compared to humic substances (508.9, 6615.9, 11352.3 μg/mL, respectively). Thus, our pilot study identified significant microRNAs for testing the in vitro anti-melanoma activity of promising drugs and melanoma diagnostics in patients. Using human melanoma cell cultures gives opportunities to test new drugs on a culture that has a microRNA profile similar to that of patients with melanoma, unlike, for example, murine melanoma cell cultures. It is necessary to conduct further studies with a large number of volunteers, which will make it possible to correlate the profile of individual microRNAs with specific patient data, including the correlation of the microRNA profile with the stage of melanoma. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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14 pages, 2768 KiB

Open AccessArticle

Circulating microRNA Biomarker for Detecting Breast Cancer in High-Risk Benign Breast Tumors

by Vedbar S. Khadka, Masaki Nasu, Youping Deng and Mayumi Jijiwa

Int. J. Mol. Sci. 2023, 24(8), 7553; https://doi.org/10.3390/ijms24087553 - 20 Apr 2023

Cited by 6 | Viewed by 2691

Abstract

High-risk benign breast tumors are known to develop breast cancer at high rates. However, it is still controversial whether they should be removed during diagnosis or followed up until cancer development becomes evident. Therefore, this study sought to identify circulating microRNAs (miRNAs) that [...] Read more.

High-risk benign breast tumors are known to develop breast cancer at high rates. However, it is still controversial whether they should be removed during diagnosis or followed up until cancer development becomes evident. Therefore, this study sought to identify circulating microRNAs (miRNAs) that could serve as detection markers of cancers arising from high-risk benign tumors. Small RNA-seq was performed using plasma samples collected from patients with early-stage breast cancer (CA) and high-risk (HB), moderate-risk (MB), and no-risk (Be) benign breast tumors. Proteomic profiling of CA and HB plasma was performed to investigate the underlying functions of the identified miRNAs. Our findings revealed that four miRNAs, hsa-mir-128-3p, hsa-mir-421, hsa-mir-130b-5p, and hsa-mir-28-5p, were differentially expressed in CA vs. HB and had diagnostic power to discriminate CA from HB with AUC scores greater than 0.7. Enriched pathways based on the target genes of these miRNAs indicated their association with IGF-1. Furthermore, the Ingenuity Pathway Analysis performed on the proteomic data revealed that the IGF-1 signaling pathway was significantly enriched in CA vs. HB. In conclusion, these findings suggest that these miRNAs could potentially serve as biomarkers for detecting early-stage breast cancer from high-risk benign tumors by monitoring IGF signaling-induced malignant transformation. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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Review

Jump to: Editorial, Research

28 pages, 1292 KiB

Open AccessReview

Use of microRNAs as Diagnostic, Prognostic, and Therapeutic Tools for Glioblastoma

by David Valle-Garcia, Verónica Pérez de la Cruz, Itamar Flores, Aleli Salazar, Benjamín Pineda and Karla F. Meza-Sosa

Int. J. Mol. Sci. 2024, 25(5), 2464; https://doi.org/10.3390/ijms25052464 - 20 Feb 2024

Cited by 5 | Viewed by 2560

Abstract

Glioblastoma (GB) is the most aggressive and common type of cancer within the central nervous system (CNS). Despite the vast knowledge of its physiopathology and histology, its etiology at the molecular level has not been completely understood. Thus, attaining a cure has not [...] Read more.

Glioblastoma (GB) is the most aggressive and common type of cancer within the central nervous system (CNS). Despite the vast knowledge of its physiopathology and histology, its etiology at the molecular level has not been completely understood. Thus, attaining a cure has not been possible yet and it remains one of the deadliest types of cancer. Usually, GB is diagnosed when some symptoms have already been presented by the patient. This diagnosis is commonly based on a physical exam and imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI), together with or followed by a surgical biopsy. As these diagnostic procedures are very invasive and often result only in the confirmation of GB presence, it is necessary to develop less invasive diagnostic and prognostic tools that lead to earlier treatment to increase GB patients’ quality of life. Therefore, blood-based biomarkers (BBBs) represent excellent candidates in this context. microRNAs (miRNAs) are small, non-coding RNAs that have been demonstrated to be very stable in almost all body fluids, including saliva, serum, plasma, urine, cerebrospinal fluid (CFS), semen, and breast milk. In addition, serum-circulating and exosome-contained miRNAs have been successfully used to better classify subtypes of cancer at the molecular level and make better choices regarding the best treatment for specific cases. Moreover, as miRNAs regulate multiple target genes and can also act as tumor suppressors and oncogenes, they are involved in the appearance, progression, and even chemoresistance of most tumors. Thus, in this review, we discuss how dysregulated miRNAs in GB can be used as early diagnosis and prognosis biomarkers as well as molecular markers to subclassify GB cases and provide more personalized treatments, which may have a better response against GB. In addition, we discuss the therapeutic potential of miRNAs, the current challenges to their clinical application, and future directions in the field. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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32 pages, 1299 KiB

Open AccessReview

HCC-Related lncRNAs: Roles and Mechanisms

by Mimansha Shah and Devanand Sarkar

Int. J. Mol. Sci. 2024, 25(1), 597; https://doi.org/10.3390/ijms25010597 - 2 Jan 2024

Cited by 11 | Viewed by 3138

Abstract

Hepatocellular carcinoma (HCC) presents a significant global health threat, particularly in regions endemic to hepatitis B and C viruses, and because of the ongoing pandemic of obesity causing metabolic-dysfunction-related fatty liver disease (MAFLD), a precursor to HCC. The molecular intricacies of HCC, genetic [...] Read more.

Hepatocellular carcinoma (HCC) presents a significant global health threat, particularly in regions endemic to hepatitis B and C viruses, and because of the ongoing pandemic of obesity causing metabolic-dysfunction-related fatty liver disease (MAFLD), a precursor to HCC. The molecular intricacies of HCC, genetic and epigenetic alterations, and dysregulated signaling pathways facilitate personalized treatment strategies based on molecular profiling. Epigenetic regulation, encompassing DNA methyltion, histone modifications, and noncoding RNAs, functions as a critical layer influencing HCC development. Long noncoding RNAs (lncRNAs) are spotlighted for their diverse roles in gene regulation and their potential as diagnostic and therapeutic tools in cancer. In this review, we explore the pivotal role of lncRNAs in HCC, including MAFLD and viral hepatitis, the most prevalent risk factors for hepatocarcinogenesis. The dysregulation of lncRNAs is implicated in HCC progression by modulating chromatin regulation and transcription, sponging miRNAs, and influencing structural functions. The ongoing studies on lncRNAs contribute to a deeper comprehension of HCC pathogenesis and offer promising routes for precision medicine, highlighting the utility of lncRNAs as early biomarkers, prognostic indicators, and therapeutic targets. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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26 pages, 1358 KiB

Open AccessReview

The Role of EMT-Related lncRNAs in Ovarian Cancer

by Dimitra Ioanna Lampropoulou, Marios Papadimitriou, Christos Papadimitriou, Dimitrios Filippou, Georgia Kourlaba, Gerasimos Aravantinos and Maria Gazouli

Int. J. Mol. Sci. 2023, 24(12), 10079; https://doi.org/10.3390/ijms241210079 - 13 Jun 2023

Cited by 4 | Viewed by 2800

Abstract

Ovarian cancer (OC) is one of the deadliest cancers worldwide; late diagnosis and drug resistance are two major factors often responsible for high morbidity and treatment failure. Epithelial-to-mesenchymal transition (EMT) is a dynamic process that has been closely linked with cancer. Long non-coding [...] Read more.

Ovarian cancer (OC) is one of the deadliest cancers worldwide; late diagnosis and drug resistance are two major factors often responsible for high morbidity and treatment failure. Epithelial-to-mesenchymal transition (EMT) is a dynamic process that has been closely linked with cancer. Long non-coding RNAs (lncRNAs) have been also associated with several cancer-related mechanisms, including EMT. We conducted a literature search in the PubMed database in order to sum up and discuss the role of lncRNAs in regulating OC-related EMT and their underlying mechanisms. Seventy (70) original research articles were identified, as of 23 April 2023. Our review concluded that the dysregulation of lncRNAs is highly associated with EMT-mediated OC progression. A comprehensive understanding of lncRNAs’ mechanisms in OC will help in identifying novel and sensitive biomarkers and therapeutic targets for this malignancy. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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32 pages, 3675 KiB

Open AccessReview

Regulation of the Cell Cycle by ncRNAs Affects the Efficiency of CDK4/6 Inhibition

by Qingyi Hu and Tao Huang

Int. J. Mol. Sci. 2023, 24(10), 8939; https://doi.org/10.3390/ijms24108939 - 18 May 2023

Cited by 6 | Viewed by 5188

Abstract

Cyclin-dependent kinases (CDKs) regulate cell division at multiple levels. Aberrant proliferation induced by abnormal cell cycle is a hallmark of cancer. Over the past few decades, several drugs that inhibit CDK activity have been created to stop the development of cancer cells. The [...] Read more.

Cyclin-dependent kinases (CDKs) regulate cell division at multiple levels. Aberrant proliferation induced by abnormal cell cycle is a hallmark of cancer. Over the past few decades, several drugs that inhibit CDK activity have been created to stop the development of cancer cells. The third generation of selective CDK4/6 inhibition has proceeded into clinical trials for a range of cancers and is quickly becoming the backbone of contemporary cancer therapy. Non-coding RNAs, or ncRNAs, do not encode proteins. Many studies have demonstrated the involvement of ncRNAs in the regulation of the cell cycle and their abnormal expression in cancer. By interacting with important cell cycle regulators, preclinical studies have demonstrated that ncRNAs may decrease or increase the treatment outcome of CDK4/6 inhibition. As a result, cell cycle-associated ncRNAs may act as predictors of CDK4/6 inhibition efficacy and perhaps present novel candidates for tumor therapy and diagnosis. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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26 pages, 1123 KiB

Open AccessReview

Interplay between LncRNAs and microRNAs in Breast Cancer

by Heidi Schwarzenbach and Peter B. Gahan

Int. J. Mol. Sci. 2023, 24(9), 8095; https://doi.org/10.3390/ijms24098095 - 30 Apr 2023

Cited by 14 | Viewed by 2617

Abstract

(1) Although long noncoding RNAs (lncRNAs) are known to be precursors of microRNAs (miRNAs), they frequently act as competing endogoneous RNAs (ceRNAs), yet still their interplay with miRNA is not well known. However, their interaction with miRNAs may result in the modulation of [...] Read more.

(1) Although long noncoding RNAs (lncRNAs) are known to be precursors of microRNAs (miRNAs), they frequently act as competing endogoneous RNAs (ceRNAs), yet still their interplay with miRNA is not well known. However, their interaction with miRNAs may result in the modulation of miRNA action. (2) To determine the contribution of these RNA molecules in tumor resistance to chemotherapeutic drugs, it is essential to consider not only the oncogenic and tumor suppressive function of miRNAs but also the impact of lncRNAs on miRNAs. Therefore, we performed an extensive search in different databases including PubMed. (3) The present study concerns the interplay between lncRNAs and miRNAs in the regulatory post-transcriptional network and their impact on drugs used in the treatment of breast cancer. (4) Consideration of this interplay may improve the search for new drugs to circumvent chemoresistance. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches

by Evangelos Koustas, Eleni-Myrto Trifylli, Panagiotis Sarantis, Nikolaos Papadopoulos, Konstantinos Papanikolopoulos, Georgios Aloizos, Christos Damaskos, Nikolaos Garmpis, Anna Garmpi, Dimitris Matthaios and Michalis V. Karamouzis

Int. J. Mol. Sci. 2023, 24(8), 7168; https://doi.org/10.3390/ijms24087168 - 12 Apr 2023

Cited by 8 | Viewed by 2329

Abstract

Hepatocellular carcinoma (HCC) constitutes a frequent highly malignant form of primary liver cancer and is the third cause of death attributable to malignancy. Despite the improvement in the therapeutic strategies with the exploration of novel pharmacological agents, the survival rate for HCC is [...] Read more.

Hepatocellular carcinoma (HCC) constitutes a frequent highly malignant form of primary liver cancer and is the third cause of death attributable to malignancy. Despite the improvement in the therapeutic strategies with the exploration of novel pharmacological agents, the survival rate for HCC is still low. Shedding light on the multiplex genetic and epigenetic background of HCC, such as on the emerging role of microRNAs, is considered quite promising for the diagnosis and the prediction of this malignancy, as well as for combatting drug resistance. MicroRNAs (miRNAs) constitute small noncoding RNA sequences, which play a key role in the regulation of several signaling and metabolic pathways, as well as of pivotal cellular functions such as autophagy, apoptosis, and cell proliferation. It is also demonstrated that miRNAs are significantly implicated in carcinogenesis, either acting as tumor suppressors or oncomiRs, while aberrations in their expression levels are closely associated with tumor growth and progression, as well as with local invasion and metastatic dissemination. The arising role of miRNAs in HCC is in the spotlight of the current scientific research, aiming at the development of novel therapeutic perspectives. In this review, we will shed light on the emerging role of miRNAs in HCC. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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