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Cells
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Long Non-coding RNAs in Cancer Metastasis
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Long Non-coding RNAs in Cancer Metastasis

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell and Gene Therapy".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 15089

Special Issue Editors

Prof. Dr. Lei Shi

E-Mail Website
Guest Editor
School of Public Health, Lanzhou University, Lanzhou 730000, China
Interests: lncRNAs; tumor microenvironment; KRAS pathway; metastasis
Prof. Dr. Bolin Liu

E-Mail Website
Guest Editor
Department of Genetics, Stanley S. Scott Cancer Center, New Orleans, LA, USA
Interests: receptor tyrosine kinase (RTK); cell signaling; cell cycle; apoptosis; drug resistance; tumor metastasis; targeted therapy; experimental therapeutics; epigenetic regulation of gene expression; ncRNAs (miRNA and lncRNA); breast cancer; non-small lung cancer (NSCLC)
Dr. Xiaolong Shi

E-Mail Website
Guest Editor
Department of Experimental Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China
Interests: non-coding RNA; EMT; tumor metastasis
Dr. Xueli Zhang

E-Mail Website1 Website2
Guest Editor
Shanghai Cancer Institute, Shanghai, China
Interests: tumor immune microenvironment; digestive system neoplasms

Special Issue Information

Dear Colleagues,

Long non-coding RNAs (lncRNAs) are classified as RNA transcripts longer than 200 nucleotides and do not encode proteins. LncRNAs exert critical functions in gene regulation by altering gene levels, mRNA alternative splicing, and transcriptional and translational regulation. LncRNAs are dysregulated in a variety of malignant tumors. Growing evidence indicates that their abnormal expression can contribute to cell proliferation/growth, influence the tumor microenvironment, shape the immune response, and modulate migration/invasion and epithelial-mesenchymal transition, which eventually promote or inhibit tumor metastasis.

This Special Issue focuses on the topic relevant to lncRNA in cancer initiation, development, and metastasis via multiple pathways using state-of-the-art methodologies. Bioinformatic analysis, clinical samples, and animal models, in particular, the PDX model or gene knock-out mouse model are appreciated. It will present an update on our knowledge of the underlying molecular features and biological mechanisms of lncRNAs, including epigenetics, chromatin modulation, in-trans or in-cis gene regulation, and antitumor immunity. We invite original contributions, as well as review articles that bring novel insights to help us better understand the fascinating world of lncRNA in cancer metastasis.

We look forward to your contributions.

Prof. Dr. Lei Shi
Prof. Dr. Bolin Liu
Dr. Xiaolong Shi
Dr. Xueli Zhang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lncRNA
  • RNA binding protein
  • tumor metastasis
  • antitumor immunity
  • tumor microenvironment

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Published Papers (5 papers)

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Research

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14 pages, 1869 KiB  
Article
Hypoxia-Regulated lncRNA USP2-AS1 Drives Head and Neck Squamous Cell Carcinoma Progression
by Jianmin Tang, Zheng Wu, Xiaohang Wang, Yanli Hou, Yongrui Bai and Ye Tian
Cells 2022, 11(21), 3407; https://doi.org/10.3390/cells11213407 - 28 Oct 2022
Cited by 4 | Viewed by 2211
Abstract
The role of hypoxia-regulated long non-coding RNA (lncRNA) in the development of head and neck squamous cell carcinoma (HNSCC) remains to be elucidated. In the current study, we initially screened hypoxia-regulated lncRNA in HNSCC cells by RNA-seq, before focusing on the rarely annotated [...] Read more.
The role of hypoxia-regulated long non-coding RNA (lncRNA) in the development of head and neck squamous cell carcinoma (HNSCC) remains to be elucidated. In the current study, we initially screened hypoxia-regulated lncRNA in HNSCC cells by RNA-seq, before focusing on the rarely annotated lncRNA USP2 antisense RNA 1 (USP2-AS1). We determined that USP2-AS1 is a direct target of HIF1α and is remarkably elevated in HNSCC compared with matched normal tissues. Patients with a higher level of USP2-AS1 suffered a poor prognosis. Next, loss- and gain-of-function assays revealed that USP2-AS1 promoted cell proliferation and invasion in vitro and in vivo. Mechanically, RNA pulldown and LC–MS/MS demonstrated that the E3 ligase DDB1- and CUL4-associated factor 13 (DCAF13) is one of the binding partners to USP2-AS1 in HNSCC cells. In addition, we assumed that USP2-AS1 regulates the activity of DCAF13 by targeting its substrate ATR. Moreover, the knockdown of DCAF13 restored the elevated cell proliferation and growth levels achieved by USP2-AS1 overexpression. Altogether, we found that lncRNA USP2-AS1 functions as a HIF1α-regulated oncogenic lncRNA and promotes HNSCC cell proliferation and growth by interacting and modulating the activity of DCAF13. Full article
(This article belongs to the Special Issue Long Non-coding RNAs in Cancer Metastasis)
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19 pages, 4236 KiB  
Article
Prognostic Profiling of the EMT-Associated and Immunity-Related LncRNAs in Lung Squamous Cell Carcinomas
by Qifeng Sun, Yan Gao, Yehui Zhang, Hongmei Cao, Jiajia Liu, Shi-Yong Neo, Keguang Chen, Yanping Bi and Jing Wu
Cells 2022, 11(18), 2881; https://doi.org/10.3390/cells11182881 - 15 Sep 2022
Cited by 5 | Viewed by 2277
Abstract
Lung squamous cell carcinoma (Lung SCC) is associated with metastatic disease, resulting in poor clinical prognosis and a low survival rate. The aberrant epithelial–mesenchymal transition (EMT) and long non-coding RNA (LncRNA) are critical attributors to tumor metastasis and invasiveness in Lung SCC. The [...] Read more.
Lung squamous cell carcinoma (Lung SCC) is associated with metastatic disease, resulting in poor clinical prognosis and a low survival rate. The aberrant epithelial–mesenchymal transition (EMT) and long non-coding RNA (LncRNA) are critical attributors to tumor metastasis and invasiveness in Lung SCC. The present study divided lncRNAs into two subtypes, C1 and C2 (Cluster 1 and Cluster 2), according to the correlation of EMT activity within the public TCGA and GEO databases. Subsequently, the differential clinical characteristics, mutations, molecular pathways and immune cell deconvolution between C1 and C2 were evaluated. Lastly, we further identified three key lncRNAs (DNM3OS, MAGI2-AS3 and LINC01094) that were associated with EMT and, at the same time, prognostic for the clinical outcomes of Lung SCC patients. Our study may provide a new paradigm of metastasis-associated biomarkers for predicting the prognosis of Lung SCC. Full article
(This article belongs to the Special Issue Long Non-coding RNAs in Cancer Metastasis)
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18 pages, 5973 KiB  
Article
A Novel m6A-Related LncRNA Signature for Predicting Prognosis, Chemotherapy and Immunotherapy Response in Patients with Lung Adenocarcinoma
by Yefeng Shen, Shaochun Wang and Yuanzhou Wu
Cells 2022, 11(15), 2399; https://doi.org/10.3390/cells11152399 - 3 Aug 2022
Cited by 9 | Viewed by 2262
Abstract
N6-methyladenosine (m6A) and long non-coding RNA (lncRNA) have been associated with cancer prognosis and the effect of immunotherapy. However, the roles of m6A-related lncRNAs in the prognosis and immunotherapy in lung adenocarcinoma (LUAD) patients remain unclear. We evaluated the m6A modification patterns of [...] Read more.
N6-methyladenosine (m6A) and long non-coding RNA (lncRNA) have been associated with cancer prognosis and the effect of immunotherapy. However, the roles of m6A-related lncRNAs in the prognosis and immunotherapy in lung adenocarcinoma (LUAD) patients remain unclear. We evaluated the m6A modification patterns of 695 samples based on m6A regulators, and prognostic m6A-related lncRNAs were identified via a weighted gene co-expression network analysis. Twelve abnormal m6A regulators and nine prognostic lncRNAs were identified. The tumor microenvironment cell-infiltrating characteristics of three m6A-related lncRNA clusters were highly consistent with the three immune phenotypes of tumors, including immune-excluded, immune-inflamed and immune-desert phenotypes. The lncRNA score system was established, and high lncRNA score patients were associated with better overall survival. The lncRNA score was correlated with the expression of the immune checkpoints. Two immunotherapy cohorts supported that the high lncRNA score enhanced the response to anti-PD-1/L1 immunotherapy and was remarkably correlated with the inflamed immune phenotype, showing significant therapeutic advantages and clinical benefits. Furthermore, the patients with high lncRNA scores were more sensitive to erlotinib and axitinib. The lncRNA score was associated with the expression of miRNA and the regulation of post-transcription. We constructed an applied lncRNA score-system to identify eligible LUAD patients for immunotherapy and predict the sensitivity to chemotherapeutic drugs. Full article
(This article belongs to the Special Issue Long Non-coding RNAs in Cancer Metastasis)
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15 pages, 6534 KiB  
Article
ENO2 Promotes Colorectal Cancer Metastasis by Interacting with the LncRNA CYTOR and Activating YAP1-Induced EMT
by Chunwei Lv, Hongfei Yu, Keyi Wang, Chaoyi Chen, Jinlong Tang, Fengyan Han, Minglang Mai, Kehong Ye, Maode Lai and Honghe Zhang
Cells 2022, 11(15), 2363; https://doi.org/10.3390/cells11152363 - 1 Aug 2022
Cited by 21 | Viewed by 3719
Abstract
The glycolytic enzyme enolase 2 (ENO2) is dysregulated in many types of cancer. However, the roles and detailed molecular mechanism of ENO2 in colorectal cancer (CRC) metastasis remain unclear. Here, we performed a comprehensive analysis of ENO2 expression in 184 local CRC samples [...] Read more.
The glycolytic enzyme enolase 2 (ENO2) is dysregulated in many types of cancer. However, the roles and detailed molecular mechanism of ENO2 in colorectal cancer (CRC) metastasis remain unclear. Here, we performed a comprehensive analysis of ENO2 expression in 184 local CRC samples and samples from the TCGA and GEO databases and found that ENO2 upregulation in CRC samples was negatively associated with prognosis. By knocking down and overexpressing ENO2, we found that ENO2 promoted CRC cell migration and invasion, which is dependent on its interaction with the long noncoding RNA (lncRNA) CYTOR, but did not depend on glycolysis regulation. Furthermore, CYTOR mediated ENO2 binding to large tumor suppressor 1 (LATS1) and competitively inhibited the phosphorylation of Yes-associated protein 1 (YAP1), which ultimately triggered epithelial–mesenchymal transition (EMT). Collectively, these findings highlight the molecular mechanism of the ENO2–CYTOR interaction, and ENO2 could be considered a potential therapeutic target for CRC. Full article
(This article belongs to the Special Issue Long Non-coding RNAs in Cancer Metastasis)
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Review

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20 pages, 4380 KiB  
Review
Recent Clinical Advances on Long Non-Coding RNAs in Triple-Negative Breast Cancer
by Desh Deepak Singh, Hae-Jeung Lee and Dharmendra Kumar Yadav
Cells 2023, 12(4), 674; https://doi.org/10.3390/cells12040674 - 20 Feb 2023
Cited by 5 | Viewed by 3375
Abstract
Triple-negative breast cancer (TNBC) is a more aggressive type of breast cancer due to its heterogeneity and complex molecular mechanisms. TNBC has a high risk for metastasis, and it is difficult to manage clinical conditions of the patients. Various investigations are being conducted [...] Read more.
Triple-negative breast cancer (TNBC) is a more aggressive type of breast cancer due to its heterogeneity and complex molecular mechanisms. TNBC has a high risk for metastasis, and it is difficult to manage clinical conditions of the patients. Various investigations are being conducted to overcome these challenges using RNA, DNA, and proteins for early diagnosis and treatment. Recently, long non-coding RNAs (lncRNAs) have emerged as a novel target to treat the multistep process of TNBC. LncRNAs regulate epigenetic expression levels, cell proliferation and apoptosis, and tumour invasiveness and metastasis. Thus, lncRNA-based early diagnosis and treatment options could be helpful, especially for patients with severe TNBC. lncRNAs are expressed in a highly specific manner in cells and tissues and are involved in TNBC progression and development. lncRNAs could be used as sensitive and specific targets for diagnosis, treatment, and monitoring of patients with TNBC. Therefore, the exploration of novel diagnostic and prognostic biomarkers is of extreme importance. Here, we discuss the molecular advances on lncRNA regulation of TNBC and lncRNA-based early diagnosis, treatment, and drug resistance. Full article
(This article belongs to the Special Issue Long Non-coding RNAs in Cancer Metastasis)
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