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Lin Y, Zhao W, Pu R, Lv Z, Xie H, Li Y, Zhang Z. Long non‑coding RNAs as diagnostic and prognostic biomarkers for colorectal cancer (Review). Oncol Lett 2024; 28:486. [PMID: 39185489 PMCID: PMC11342420 DOI: 10.3892/ol.2024.14619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Accepted: 07/29/2024] [Indexed: 08/27/2024] Open
Abstract
Colorectal cancer (CRC) ranks as the 3rd most common cancer globally and is the 2nd leading cause of cancer-related death. Owing to the lack of specific early symptoms and the limitations of existing early diagnostic methods, most patients with CRC are diagnosed at advanced stages. To overcome these challenges, researchers have increasingly focused on molecular biomarkers, with particular interest in long non-coding RNAs (lncRNAs). These non-protein-coding RNAs, which exceed 200 nucleotides in length, play critical roles in the development and progression of CRC. The stability and detectability of lncRNAs in the circulatory system make them promising candidate biomarkers. The analysis of circulating lncRNAs in peripheral blood represents a potential option for minimally invasive diagnostic tests based on liquid biopsy samples. The present review aimed to evaluate the efficacy of lncRNAs with altered expression levels in peripheral blood as diagnostic markers for CRC. Additionally, the clinical significance of lncRNAs as prognostic markers for this disease were summarized.
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Affiliation(s)
- Yuning Lin
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
| | - Wenzhen Zhao
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
| | - Ruonan Pu
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
| | - Zhenyi Lv
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
| | - Hongyan Xie
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
| | - Ying Li
- Department of Ultrasonography, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Zhongying Zhang
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
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Lin Y, Zhao W, Lv Z, Xie H, Li Y, Zhang Z. The functions and mechanisms of long non-coding RNA in colorectal cancer. Front Oncol 2024; 14:1419972. [PMID: 39026978 PMCID: PMC11254705 DOI: 10.3389/fonc.2024.1419972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 06/18/2024] [Indexed: 07/20/2024] Open
Abstract
CRC poses a significant challenge in the global health domain, with a high number of deaths attributed to this disease annually. If CRC is detected only in its advanced stages, the difficulty of treatment increases significantly. Therefore, biomarkers for the early detection of CRC play a crucial role in improving patient outcomes and increasing survival rates. The development of a reliable biomarker for early detection of CRC is particularly important for timely diagnosis and treatment. However, current methods for CRC detection, such as endoscopic examination, blood, and stool tests, have certain limitations and often only detect cases in the late stages. To overcome these constraints, researchers have turned their attention to molecular biomarkers, which are considered a promising approach to improving CRC detection. Non-invasive methods using biomarkers such as mRNA, circulating cell-free DNA, microRNA, LncRNA, and proteins can provide more reliable diagnostic information. These biomarkers can be found in blood, tissue, stool, and volatile organic compounds. Identifying molecular biomarkers with high sensitivity and specificity for the early and safe, economic, and easily measurable detection of CRC remains a significant challenge for researchers.
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Affiliation(s)
- Yuning Lin
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China
| | - Wenzhen Zhao
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China
| | - Zhenyi Lv
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China
| | - Hongyan Xie
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China
| | - Ying Li
- Ultrasonography Department, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Zhongying Zhang
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China
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Xi T, Zhou Y, Ma S, Lu W, Sun Y, Sun C, Zhou Y. Construction of a potential long noncoding RNA prognostic model involved competitive endogenous RNA for patients with gastric cancer. Medicine (Baltimore) 2024; 103:e38458. [PMID: 38875399 PMCID: PMC11175963 DOI: 10.1097/md.0000000000038458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/11/2024] [Accepted: 05/13/2024] [Indexed: 06/16/2024] Open
Abstract
Increasing evidence has underscored the role of long noncoding RNAs (lncRNAs) make up the major proportion of the competing endogenous RNAs (ceRNAs) network and can regulate gene expression by competitively binding to miRNAs in the development and progression of tumors. Nevertheless, the role of lncRNA-mediated ceRNAs in gastric cancer (GC) and their regulatory mechanisms have not been elucidated to some extent. This study is aimed at constructing a prognostic risk model for GC based on lncRNAs. A TCGA (The Cancer Genome Atlas) dataset was analyzed using edgeR to identify differentially expressed lncRNAs (DElncRNAs) in GC tissues vs normal tissues. Subsequently, DElncRNAs that could predict GC prognosis were determined using a training set. A prognostic risk model based on the DElncRNAs was then constructed. The performance of the model was tested using a test set. The functions of these lncRNAs in GC were investigated using a lncRNA-miRNA-mRNA network. Analysis of lncRNA expression in 407 TCGA GC cases identified 3 lncRNAs that significantly correlated with prognosis. GC cases with high-risk scores showed markedly poor prognosis relative to those with low-risk scores in both the training and test sets. Univariate and multivariate Cox regression analysis of the relationship between various clinical features and prognosis found that these lncRNAs and stage significantly correlated with GC prognosis. A lncRNA-miRNA-mRNA network based on 3 lncRNAs and functional enrichment analysis of interacting mRNA indicated that these genes are enriched in various intracellular receptor signaling pathways, including regulation of muscle system process, and protein deubiquitylation. The current study provides novel insights into the lncRNA-related ceRNA network in GC and sheds lights on underlying 3 lncRNA biomarkers may be independent prognostic signatures in predicting the survival of GC patients.
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Affiliation(s)
- Tianyi Xi
- Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu Province, China
| | - Yuying Zhou
- Department of Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu Province, China
| | - Sai Ma
- Department of Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu Province, China
| | - Wen Lu
- Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu Province, China
| | - Yibin Sun
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu Province, China
| | - Chunrong Sun
- Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu Province, China
| | - Yu Zhou
- Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu Province, China
- Department of General Surgery, Second Affiliated Hospital of Soochow University, Souzhou, Jiangsu Province, China
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Luo H, Jing H, Chen W. An extensive overview of the role of lncRNAs generated from immune cells in the etiology of cancer. Int Immunopharmacol 2024; 133:112063. [PMID: 38677091 DOI: 10.1016/j.intimp.2024.112063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 04/07/2024] [Accepted: 04/08/2024] [Indexed: 04/29/2024]
Abstract
Long non-coding RNAs (lncRNAs) are involved in the control of critical tumor-suppressor and oncogenic pathways in cancer. These types of non-coding RNAs could affect both immune and cancer cells. The thorough analysis of lncRNAs derived from immune cells and the incorporation of new findings significantly advance our understanding of the complex role of lncRNAs in the context of cancer. This work highlights the promise of lncRNAs for translational therapeutic approaches while also establishing a solid foundation for comprehending the complex link between lncRNAs and cancer through a coherent narrative. The main findings of this article are that types of lncRNAs derived from immune cells, such as MM2P and MALAT1, can affect the behaviors of cancer cells, like invasion, angiogenesis, and proliferation. As research in this area grows, the therapeutic potential of targeting these lncRNAs offers promising opportunities for expanding our understanding of cancer biology and developing cutting-edge, precision-based therapies for cancer therapy.
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Affiliation(s)
- Hong Luo
- Department of Oncology, Yancheng Branch of Nanjing Drum Tower Hospital, Yancheng, Jiangsu Province, China.
| | - Hailiang Jing
- Department of Integrative Medicine, Yancheng Branch of Nanjing Drum Tower Hospital, Yancheng, Jiangsu Province, China
| | - Wei Chen
- Department of Oncology, Tumor Hospital Affiliated to Nantong University, Nantong, Jiangsu Province, China
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Wang Y, Sun N, He R, Wang Z, Jin J, Gao T, Qu J. Molecular characterization of m6A RNA methylation regulators with features of immune dysregulation in IgA nephropathy. Clin Exp Med 2024; 24:92. [PMID: 38693353 PMCID: PMC11062981 DOI: 10.1007/s10238-024-01346-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 04/02/2024] [Indexed: 05/03/2024]
Abstract
The role of RNA N6-methyladenosine (m6A) modification in immunity is being elucidated. This study aimed to explore the potential association between m6A regulators and the immune microenvironment in IgA nephropathy (IgAN). The expression profiles of 24 m6A regulators in 107 IgAN patients were obtained from the Gene Expression Omnibus (GEO) database. The least absolute shrinkage and selection operator (LASSO) regression and logistic regression analysis were utilized to construct a model for distinguishing IgAN from control samples. Based on the expression levels of m6A regulators, unsupervised clustering was used to identify m6A-induced molecular clusters in IgAN. Gene set enrichment analysis (GSEA) and immunocyte infiltration among different clusters were examined. The gene modules with the highest correlation for each of the three clusters were identified by weighted gene co-expression network analysis (WGCNA). A model containing 10 m6A regulators was developed using LASSO and logistic regression analyses. Three molecular clusters were determined using consensus clustering of 24 m6A regulators. A decrease in the expression level of YTHDF2 in IgAN samples was significantly negatively correlated with an increase in resting natural killer (NK) cell infiltration and was positively correlated with the abundance of M2 macrophage infiltration. The risk scores calculated by the nomogram were significantly higher for cluster-3, and the expression levels of m6A regulators in this cluster were generally low. Immunocyte infiltration and pathway enrichment results for cluster-3 differed significantly from those for the other two clusters. Finally, the expression of YTHDF2 was significantly decreased in IgAN based on immunohistochemical staining. This study demonstrated that m6A methylation regulators play a significant role in the regulation of the immune microenvironment in IgAN. Based on m6A regulator expression patterns, IgAN can be classified into multiple subtypes, which might provide additional insights into novel therapeutic methods for IgAN.
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Affiliation(s)
- Yihao Wang
- Department of Nephrology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China
| | - Nan Sun
- Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Rui He
- Shanghai Immune Therapy Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Zida Wang
- Department of Emergency, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Jingsi Jin
- Shanghai Immune Therapy Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Ting Gao
- Department of Emergency, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
| | - Junwen Qu
- Department of Urology, Jiading Branch, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201899, China.
- Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
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6
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Swaminathan G, Rogel-Ayala DG, Armich A, Barreto G. Implications in Cancer of Nuclear Micro RNAs, Long Non-Coding RNAs, and Circular RNAs Bound by PRC2 and FUS. Cancers (Basel) 2024; 16:868. [PMID: 38473229 DOI: 10.3390/cancers16050868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 02/13/2024] [Accepted: 02/16/2024] [Indexed: 03/14/2024] Open
Abstract
The eukaryotic genome is mainly transcribed into non-coding RNAs (ncRNAs), including different RNA biotypes, such as micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), among others. Although miRNAs are assumed to act primarily in the cytosol, mature miRNAs have been reported and functionally characterized in the nuclei of different cells. Further, lncRNAs are important regulators of different biological processes in the cell nucleus as part of different ribonucleoprotein complexes. CircRNAs constitute a relatively less-characterized RNA biotype that has a circular structure as result of a back-splicing process. However, circRNAs have recently attracted attention in different scientific fields due to their involvement in various biological processes and pathologies. In this review, we will summarize recent studies that link to cancer miRNAs that have been functionally characterized in the cell nucleus, as well as lncRNAs and circRNAs that are bound by core components of the polycomb repressive complex 2 (PRC2) or the protein fused in sarcoma (FUS), highlighting mechanistic aspects and their diagnostic and therapeutic potential.
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Affiliation(s)
| | - Diana G Rogel-Ayala
- Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, F-54000 Nancy, France
- Lung Cancer Epigenetics, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
| | - Amine Armich
- Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, F-54000 Nancy, France
| | - Guillermo Barreto
- Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, F-54000 Nancy, France
- Lung Cancer Epigenetics, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
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Liang W, Zhao Y, Meng Q, Jiang W, Deng S, Xue J. The role of long non-coding RNA in hepatocellular carcinoma. Aging (Albany NY) 2024; 16:4052-4073. [PMID: 38334963 PMCID: PMC10929815 DOI: 10.18632/aging.205523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 12/12/2023] [Indexed: 02/10/2024]
Abstract
Hepatocellular carcinoma (HCC) is a prevalent liver malignancy with complex etiology and generally poor prognosis. Recently, long non-coding RNAs (lncRNAs), non-protein-coding RNA molecules exceeding 200 nucleotides, have emerged as pivotal players in HCC, influencing its initiation, progression, invasion, and metastasis. These lncRNAs modulate gene expression at epigenetic, transcriptional, and post-transcriptional levels, actively participating in the pathological and physiological processes of HCC. Understanding the intricate relationship between lncRNAs and HCC is important for improving prognosis and reducing mortality. This review summarizes advancements in elucidating the role of lncRNAs in HCC pathogenesis.
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Affiliation(s)
- Weizheng Liang
- Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
- Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
- Tumor Research Institute, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
| | - Yan Zhao
- Department of Mathematics and Computer Science, Free University Berlin, Berlin 14195, Germany
| | - Qingxue Meng
- Technology Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
| | - Wenjie Jiang
- Department of Artificial Intelligence and Data Science, Hebei University of Technology, Tianjin 300401, China
| | - Shoulong Deng
- National Health Commission of China (NHC) Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China
| | - Jun Xue
- Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
- Tumor Research Institute, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
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Quan ZH, Xu FP, Huang Z, Chen RH, Xu QW, Lin L. LncRNA MYLK antisense RNA 1 activates cell division cycle 42/Neutal Wiskott-Aldrich syndrome protein pathway via microRNA-101-5p to accelerate epithelial-to-mesenchymal transition of colon cancer cells. Kaohsiung J Med Sci 2024; 40:11-22. [PMID: 37950620 DOI: 10.1002/kjm2.12773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 09/13/2023] [Accepted: 09/20/2023] [Indexed: 11/13/2023] Open
Abstract
Long noncoding RNA MYLK antisense RNA 1 (MYLK-AS1) is the crux in multiple diseases. Therefore, the purpose of this study was to investigate the possible mechanism of MYLK-AS1. A total of 62 colon cancer (CC) specimens and paired adjacent normal tissues were collected, and the expression of MYLK-AS1, microRNA (miR)-101-5p/cell division cycle 42 (CDC42) was detected. CC cell lines were transfected with MYLK-AS1, miR-101-5p, CDC42-related plasmids, and the biological functions and markers of epithelial-mesenchymal transition (EMT) were analyzed. The binding relationship between MYLK-AS1, miR-101-5p, and CDC42 was evaluated. In CC tissues and cell lines, MYLK-AS1 and CDC42 were highly expressed, and miR-101-5p was lowly expressed. Inhibition of MYLK-AS1 or upregulation of miR-101-5p can inhibit CC cell growth and EMT. miR-101-5p inhibited CDC42/N-wasp axis activation in CC cells by targeting CDC42. Knockdown of CDC42 or upregulation of miR-101-5p partially reversed the effects caused by upregulation of MYLK-AS1. MYLK-AS1, which is significantly upregulated in CC, may be a molecular sponge for miR-101-5p, and MYLK-AS1 promotes the activation of the CDC42/N-wasp axis in CC cells by targeting CDC42 through miR-101-5p, which in turn promotes tumor development. MYLK-AS1 may be a potential biomarker and target for CC therapy.
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Affiliation(s)
- Zhen-Hao Quan
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Fei-Peng Xu
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Zhe Huang
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Ri-Hong Chen
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Qing-Wen Xu
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Lin Lin
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
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Fan H, Zhou Y, Zhang Z, Zhou G, Yuan C. ROR1-AS1: A Meaningful Long Noncoding RNA in Oncogenesis. Mini Rev Med Chem 2024; 24:1884-1893. [PMID: 38859780 DOI: 10.2174/0113895575294482240530154620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 04/27/2024] [Accepted: 05/06/2024] [Indexed: 06/12/2024]
Abstract
Long noncoding RNA (lncRNA) is a non-coding RNA with a length of more than 200 nucleotides, involved in multiple regulatory processes in vivo, and is related to the physiology and pathology of human diseases. An increasing number of experimental results suggest that when lncRNA is abnormally expressed, it results in the development of tumors. LncRNAs can be divided into five broad categories: sense, antisense, bidirectional, intronic, and intergenic. Studies have found that some antisense lncRNAs are involved in a variety of human tumorigenesis. The newly identified ROR1-AS1, which functions as an antisense RNA of ROR1, is located in the 1p31.3 region of the human genome. Recent studies have reported that abnormal expression of lncRNA ROR1-AS1 can affect cell growth, proliferation, invasion, and metastasis and increase oncogenesis and tumor spread, indicating lncRNA ROR1-AS1 as a promising target for many tumor biological therapies. In this study, the pathophysiology and molecular mechanism of ROR1-AS1 in various malignancies are discussed by retrieving the related literature. ROR1-AS1 is a cancer-associated lncRNA, and studies have found that it is either over- or underexpressed in multiple malignancies, including liver cancer, colon cancer, osteosarcoma, glioma, cervical cancer, bladder cancer, lung adenocarcinoma, and mantle cell lymphoma. Furthermore, it has been demonstrated that lncRNA ROR1-AS1 participates in proliferation, migration, invasion, and suppression of apoptosis of cancer cells. Furthermore, lncRNA ROR1-AS1 promotes the development of tumors by up-regulating or downregulating ROR1-AS1 conjugates and various pathways and miR-504, miR-4686, miR-670-3p, and miR-375 sponges, etc., suggesting that lncRNA ROR1-AS1 may be used as a marker in tumors or a potential therapeutic target for a variety of tumors.
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Affiliation(s)
- Hong Fan
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, China
- College of Basic Medical Science, China Three Gorges University, Yichang 443002, China
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, China
| | - Yunxi Zhou
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, China
- College of Basic Medical Science, China Three Gorges University, Yichang 443002, China
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, China
| | - Ziyan Zhang
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, China
- College of Basic Medical Science, China Three Gorges University, Yichang 443002, China
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, China
| | - Gang Zhou
- College of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China
- Yichang Hospital of Traditional Chinese Medicine, Yichang, 443002, China
| | - Chengfu Yuan
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, China
- College of Basic Medical Science, China Three Gorges University, Yichang 443002, China
- Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, China
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Chen P, Li Z, Liang Y, Wei M, Jiang H, Chen S, Zhao Z. Identification of Hypoxia-Associated Signature in Colon Cancer to Assess Tumor Immune Microenvironment and Predict Prognosis Based on 14 Hypoxia-Associated Genes. Int J Gen Med 2023; 16:2503-2518. [PMID: 37346810 PMCID: PMC10281280 DOI: 10.2147/ijgm.s407005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 05/30/2023] [Indexed: 06/23/2023] Open
Abstract
Purpose Colon cancer is the main malignant tumor of the digestive tract. Hypoxia is highly related to the occurrence, progression and tumor immune microenvironment (TIME) of cancer. The aim of this study was to identify a hypoxia-associated signature with high accuracy for predicting the prognosis and TIME of colon cancer. Methods Download colon cancer data from the GEO and TCGA databases. A novel hypoxia risk model was identified to predict the prognosis of colon cancer patients. Subsequently, GSEA, TIME and mutation analysis were performed in the hypoxia high and low risk score groups. Finally, the signature gene ANKZF1 was selected for functional verification at the cellular level. Results A novel hypoxia risk model was identified. The risk score was significantly associated with poorer overall survival in colon cancer, and could be used as an independent prognostic factor for colon cancer. GSEA analysis found that the processes related to stimulate tumor proliferation and anti-apoptosis were significantly enriched in the hypoxia high risk score group. The expression of immunosuppressive cells and most immune checkpoints in the high risk score group was significantly higher than that in the low risk score group. In vitro cell experiments showed that knockdown the expression of ANKZF1 could inhibit the proliferation, migration and invasion of colon cancer cells. Conclusion Hypoxia plays an important role in evaluating the TIME and predicting the prognosis of colon cancer.
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Affiliation(s)
- Peng Chen
- Department of General Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China
| | - Zhongxin Li
- Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China
| | - Yulong Liang
- Department of General Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China
| | - Ming Wei
- Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China
| | - Haibo Jiang
- Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China
| | - Shihao Chen
- Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China
| | - Zengren Zhao
- Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China
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11
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Sun S, Zou Y, Xu N, Wang K, Rong S, Lv J, Hu B, Mai Y, Zhu D, Ding L. Long non-coding RNA ATB expedites non-small cell lung cancer progression by the miR-200b/fibronectin 1 axis. J Clin Lab Anal 2023; 37:e24822. [PMID: 36806318 PMCID: PMC10020841 DOI: 10.1002/jcla.24822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 02/22/2023] Open
Abstract
BACKGROUND Long non-coding RNA (lncRNA) ATB belongs to an active modulator in multiple cancers, but its expression along with potential underlying non-small cell lung cancer (NSCLC) is obscure. Our study aimed to investigate the role and potential mechanism of LncRNA ATB in NSCLC. METHODS LncRNA ATB expression in NSCLC tissues and cell lines was detected by qRT-PCR. Effects of LncRNA ATB on NSCLC cell proliferation, migration and invasion were assessed by MTS, colony formation and transwell assays. The connection among LncRNA ATB, miR-200b and fibronectin 1 (FN1) was determined by bioformatics prediction and luciferase reporter assay. RESULTS In this research, upregulation of LncRNA ATB was discovered in NSCLC tissue samples and cell lines. LncRNA ATB was positively related to advanced tumor phase as well as lymph node metastasis. Cell function assays reflected LncRNA ATB expedited NSCLC cells proliferation, migration and invasion. LncRNA ATB promoted fibronectin 1 (FN1) expression via inhibiting miR-200b. Furthermore, LncRNA ATB depletion suppressed NSCLC cells proliferation, migration and invasion, while miR-200b inhibitor or pcDNA-FN1 rescued these effects. CONCLUSION In summary, our outcomes elucidated that LncRNA ATB/miR-200b axis expedited NSCLC cells proliferation, migration and invasion by up-regulating FN1.
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Affiliation(s)
- Shifang Sun
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Yifan Zou
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Ningjie Xu
- School of MedicineNingbo UniversityNingboChina
| | - Kaiyue Wang
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Shanshan Rong
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Jiarong Lv
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Bin Hu
- School of MedicineNingbo UniversityNingboChina
| | - Yifeng Mai
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Decai Zhu
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Liren Ding
- Department of Respiratory and Critical Care MedicineThe Second Affiliated Hospital of Zhejiang University Medical CollegeHangzhouChina
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Islam S, Mukherjee C. Molecular regulation of hypoxia through the lenses of noncoding RNAs and epitranscriptome. WILEY INTERDISCIPLINARY REVIEWS. RNA 2023; 14:e1750. [PMID: 35785444 DOI: 10.1002/wrna.1750] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 05/27/2022] [Accepted: 06/06/2022] [Indexed: 11/09/2022]
Abstract
Cells maintain homeostasis in response to environmental stress through specific cell stress responses. Hypoxic stress, well known to be associated with diverse solid tumors, is one of the main reasons for cancer-related mortality. Although cells can balance themselves well during hypoxic stress, the underlying molecular mechanisms are not well understood. The enhanced appreciation of diverse roles played by noncoding transcriptome and epigenome in recent years has brought to light the involvement of noncoding RNAs and epigenetic modifiers in hypoxic regulation. The emergence of techniques like deep sequencing has facilitated the identification of large numbers of long noncoding RNAs (lncRNAs) that are differentially regulated in various cancers. Similarly, proteomic studies have identified diverse epigenetic modifiers such as HATs, HDACs, DNMTs, polycomb groups of proteins, and their possible roles in the regulation of hypoxia. The crosstalk between lncRNAs and epigenetic modifiers play a pivotal role in hypoxia-induced cancer initiation and progression. Besides the lncRNAs, several other noncoding RNAs like circular RNAs, miRNAs, and so forth are also expressed during hypoxic conditions. Hypoxia has a profound effect on the expression of noncoding RNAs and epigenetic modifiers. Conversely, noncoding RNAs/epigenetic modifies can regulate the hypoxia signaling axis by modulating the stability of the hypoxia-inducible factors (HIFs). The focus of this review is to illustrate the molecular orchestration underlying hypoxia biology, especially in cancers, which can help in identifying promising therapeutic targets in hypoxia-induced cancers. This article is categorized under: RNA Turnover and Surveillance > Regulation of RNA Stability RNA in Disease and Development > RNA in Disease RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry.
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Affiliation(s)
- Safirul Islam
- Institute of Health Sciences (erstwhile School of Biotechnology), Presidency University, Kolkata, India
| | - Chandrama Mukherjee
- Institute of Health Sciences (erstwhile School of Biotechnology), Presidency University, Kolkata, India
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13
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Anbiyaiee A, Ramazii M, Bajestani SS, Meybodi SM, Keivan M, Khoshnam SE, Farzaneh M. The function of LncRNA-ATB in cancer. CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2023; 25:1-9. [PMID: 35597865 DOI: 10.1007/s12094-022-02848-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 04/25/2022] [Indexed: 01/07/2023]
Abstract
Cancer as a progressive and complex disease is caused by early chromosomal changes and stimulated cellular transformation. Previous studies reported that long non-coding RNAs (lncRNAs) play pivotal roles in the initiation, maintenance, and progression of cancer cells. LncRNA activated by TGF-β (ATB) has been shown to be dysregulated in different types of cancer. Aberrant expression of lncRNA-ATB plays an important role in the progression of diverse malignancies. High expression of LncRNA-ATB is associated with cancer cell growth, proliferation, metastasis, and EMT. LncRNA-ATB by targeting various signaling pathways and microRNAs (miRNAs) can trigger cancer pathogenesis. Therefore, lncRNA-ATB can be a novel target for cancer prediction and diagnosis. In this review, we will focus on the function of lncRNA-ATB in various types of human cancers.
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Affiliation(s)
- Amir Anbiyaiee
- Department of Surgery, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Ramazii
- Kerman University of Medical Sciences, University of Kerman, Kerman, Iran
| | | | | | - Mona Keivan
- Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Seyed Esmaeil Khoshnam
- Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Maryam Farzaneh
- Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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14
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Abushouk AI, Kattan SW, Ahmedah HT, Baothman E, Shaheen S, Toraih EA, Fawzy MS. Expression of oncolong noncoding RNA taurine-upregulated gene-1 in colon cancer: A clinical study supported by in silico analysis. J Cancer Res Ther 2022; 18:S374-S382. [PMID: 36510991 DOI: 10.4103/jcrt.jcrt_484_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Context Recent studies confirmed that dysregulation of long noncoding RNAs (lncRNAs) is a potential contributor to the development and progression of colon cancer. However, the prognostic value of these RNA molecules remains controversial. Aims This study aimed to investigate the expression of taurine-upregulated gene-1 (TUG1) lncRNA in colon cancer and its clinical implications. Subjects and Methods A retrospective study on 47 formalin-fixed, paraffin-embedded samples of surgically resected primary colon cancer specimens was done. Total RNA purified from the colon cancer samples and noncancer adjacent tissue sections was quantified by real-time reverse transcription-polymerase chain reaction (qRT-PCR) to assess TUG1 relative expression levels normalized to GAPDH endogenous control. Also, in silico data analysis was applied. Statistical Analysis Used The relative expression levels were calculated using the LIVAK method. The survival rates were assessed using the Kaplan-Meier curves and the Cox proportional model. P < 0.05 was considered statistically significant. Results TUG1expression in the colon cancer specimens was significantly overexpressed (median = 21.50, interquartile range [IQR]: 7.0-209.2; P = 0.001) relative to the noncancerous tissues. In silico analysis confirmed TUG1 upregulation in colon carcinoma (median = 13.92, IQR: 13.5-1432). There were no significant associations between TUG1 expression and clinicopathological characteristics, such as the site, grade, stage, histopathological type, or the rates of lymphovascular invasion and relapse. Similarly, Kaplan-Meir and Cox multivariate regression analyses showed that TUG1 expression could not predict the overall survival and progression-free survival in colon cancer patients of our population. Conclusions This study confirms the overexpression of TUG1 lncRNA in colon cancer tissues. Larger sample size is warranted to further elucidate the specific role of TUG1 in colon cancer.
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Affiliation(s)
| | - Shahad W Kattan
- Department of Medical Laboratory, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia
| | - Hanadi T Ahmedah
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Rabegh, Saudi Arabia
| | - Eshrag Baothman
- Department of Medicine, Batterjee Medical Technology College, Jeddah, Saudi Arabia
| | - Sameerah Shaheen
- Anatomy Department and Stem Cell Unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Eman A Toraih
- Department of Surgery, Tulane University, School of Medicine, New Orleans, Louisiana, USA; Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Manal Said Fawzy
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Department of Biochemistry, Faculty of Medicine, Northern Border University, Saudi Arabia
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Tang J, Zhao X, Wei W, Liu W, Fan H, Liu XP, Li Y, Wang L, Guo J. METTL16-mediated translation of CIDEA promotes non-alcoholic fatty liver disease progression via m6A-dependent manner. PeerJ 2022; 10:e14379. [PMID: 36518278 PMCID: PMC9744165 DOI: 10.7717/peerj.14379] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 10/20/2022] [Indexed: 12/05/2022] Open
Abstract
Background As the most prevalent chemical modifications on eukaryotic mRNAs, N6-methyladenosine (m6A) methylation was reported to participate in the regulation of various metabolic diseases. This study aimed to investigate the roles of m6A methylation and methyltransferase-like16 (METTL16) in non-alcoholic fatty liver disease (NAFLD). Methods In this study, we used a model of diet-induced NAFLD, maintaining six male C57BL/6J mice on high-fat diet (HFD) to generate hepatic steatosis. The high-throughput sequencing and RNA sequencing were performed to identify the m6A methylation patterns and differentially expressed mRNAs in HFD mice livers. Furthermore, we detected the expression levels of m6A modify enzymes by qRT-PCR in liver tissues, and further investigated the potential role of METTL16 in NAFLD through constructing overexpression and a knockdown model of METTL16 in HepG2 cells. Results In total, we confirmed 15,999 m6A recurrent peaks in HFD mice and 12,322 in the control. Genes with differentially methylated m6A peaks were significantly associated with the dysregulated glucolipid metabolism and aggravated hepatic inflammatory response. In addition, we identified five genes (CIDEA, THRSP, OSBPL3, GDF15 and LGALS1) that played important roles in NAFLD progression after analyzing the differentially expressed genes containing differentially methylated m6A peaks. Intriguingly, we found that the expression levels of METTL16 were substantially increased in the NAFLD model in vivo and in vitro, and further confirmed that METTL16 upregulated the expression level of lipogenic genes CIDEA in HepG2 cells. Conclusions These results indicate the critical roles of m6A methylation and METTL16 in HFD-induced mice and cell NAFLD models, which broaden people's perspectives on potential m6A-related treatments and biomarkers for NAFLD.
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Affiliation(s)
- Jinhong Tang
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China,Current Affiliation: Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, P.R. China
| | - Xiangyun Zhao
- Digestive Endoscopic Center, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Wei Wei
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Weiwei Liu
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Huining Fan
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Xiu ping Liu
- Department of Gastroenterology, Shanghai Fudan University Affiliated Fifth People’s Hospital, Shanghai, China
| | - Yungai Li
- Department of Clinical Laboratory, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Long Wang
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Jinghui Guo
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
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Wang W, Zhao J, Zhang C, Zhang W, Jin M, Shao Y. Current advances in the selection of adjuvant radiotherapy regimens for keloid. Front Med (Lausanne) 2022; 9:1043840. [DOI: 10.3389/fmed.2022.1043840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 10/20/2022] [Indexed: 11/10/2022] Open
Abstract
Keloid is a common benign skin tumor in the outpatient department, and patients are often accompanied by itching and pain. Since the pathogenesis is unknown, the effect of single method treatment is unsatisfactory, and therefore the recurrence rate is high. Therefore, comprehensive treatment is mostly used in clinical treatment. Adjuvant radiotherapy is currently one of the most effective treatments for keloid. After long-term clinical practice, brachytherapy and electron beam radiotherapy has increasingly become the gold standard of treatment, because brachytherapy provides more focused radiation treatment to focal tissue to significantly reduce recurrence rate, and better preserve normal tissue. With the development of new radiotherapy techniques, more options for the treatment of keloid. Currently, adjuvant radiotherapy has been widely recognized, but there is no consensus on the optimal protocol for adjuvant radiotherapy for keloids. This review provides a review of published treatment options and new radiotherapy techniques for adjuvant radiotherapy of keloids and gives a comprehensive evaluation for clinical treatment.
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Xiaotan Sanjie Decoction Inhibits Gastric Cancer Cell Proliferation, Migration, and Invasion through lncRNA-ATB and miR-200A. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7029182. [PMID: 36060143 PMCID: PMC9436559 DOI: 10.1155/2022/7029182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 07/08/2022] [Accepted: 07/11/2022] [Indexed: 11/24/2022]
Abstract
This study is aimed at exploring whether Xiaotan Sanjie decoction (XTSJ) inhibits gastric cancer (GC) proliferation and metastasis by regulating lncRNA-ATB expression. qRT-PCR and Western blot were used to analyze lncRNA-ATB and downstream-regulated genes/proteins in human GC cells. CCK8, Edu, and flow cytometry assays were used to detect the inhibitory effect of XTSJ on cell proliferation and apoptosis. Moreover, transwell and wound healing assays were used to detect the inhibitory effect of XTSJ on migration and invasion. qRT-PCR and Western blot were used to detect regulated genes and proteins levels. The HGC-27 cell line was used for follow-up analysis due to the high level of lncRNA-ATB and cell characteristics. XTSJ inhibited the proliferation and metastasis of HGC-27 in a dose-dependent manner. Further research found that XTSJ downregulated lncRNA-ATB, Vimentin, and N-cadherin, while it upregulated miR-200a and E-cadherin in a dose-dependent manner. XTSJ also upregulated Caspase 3, Caspase 9, Bax, and downregulated Bcl-2. Furthermore, XTSJ inhibited tumor growth in vivo and downregulated EMT signaling pathways. These results indicate that XTSJ may affect EMT and Bcl-2 signaling pathways by regulating lncRNA-ATB and miR-200a, thus inhibiting proliferation, migration, and invasion of HGC-27 cells. Therefore, XTSJ may be an effective treatment for the high levels of lncRNA-ATB in GC.
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Yu X, Zhu X, Xu H, Li L. Emerging roles of long non-coding RNAs in keloids. Front Cell Dev Biol 2022; 10:963524. [PMID: 36046343 PMCID: PMC9421354 DOI: 10.3389/fcell.2022.963524] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/22/2022] [Indexed: 11/30/2022] Open
Abstract
Keloids are pathologic wound healing conditions caused by fibroblast hyperproliferation and excess collagen deposition following skin injury or irritation, which significantly impact patients by causing psychosocial and functional distress. Extracellular matrix (ECM) deposition and human fibroblast proliferation represents the main pathophysiology of keloid. Long non-coding RNAs (LncRNAs) play important roles in many biological and pathological processes, including development, differentiation and carcinogenesis. Recently, accumulating evidences have demonstrated that deregulated lncRNAs contribute to keloids formation. The present review summarizes the researches of deregulated lncRNAs in keloid. Exploring lncRNA-based methods hold promise as new effective therapies against keloid.
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Tong F, Xu L, Xu S, Zhang M. Identification of an autophagy-related 12-lncRNA signature and evaluation of NFYC-AS1 as a pro-cancer factor in lung adenocarcinoma. Front Genet 2022; 13:834935. [PMID: 36105077 PMCID: PMC9466988 DOI: 10.3389/fgene.2022.834935] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 07/11/2022] [Indexed: 11/13/2022] Open
Abstract
Objective: To develop an autophagy-related lncRNA-based risk signature and corresponding nomogram to predict overall survival (OS) for LUAD patients and investigate the possible meaning of screened factors.Methods: Differentially expressed lncRNAs and autophagy genes were screened between normal and LUAD tumor samples from the TCGA LUAD dataset. Univariate and multivariate Cox regression analyses were performed to construct the lncRNA-based risk signature and nomogram incorporating clinical information. Then, the accuracy and sensitivity were confirmed by the AUC of ROC curves in both training and validation cohorts. qPCR, immunoblot, shRNA, and ectopic expression were used to verify the positive regulation of NFYC-AS1 on BIRC6. CCK-8, immunofluorescence, and flow cytometry were used to confirm the influence of NFYC-AS1 on cell proliferation, autophagy, and apoptosis via BIRC6.Results: A 12-lncRNA risk signature and a nomogram combining related clinical information were constructed. Furthermore, the abnormal increase of NFYC-AS1 may promote LUAD progression through the autophagy-related gene BIRC6.Conclusion: 12-lncRNA signature may function as a predictive marker for LUAD patients, and NFYC-AS1 along with BIRC6 may function as carcinogenic factors in a combinatorial manner.
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Affiliation(s)
- Fang Tong
- Department of Medical Immunology, School of Medicine, Anhui University of Science and Technology, Anhui, China
- Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, Anhui, China
| | - Lifa Xu
- Department of Medical Immunology, School of Medicine, Anhui University of Science and Technology, Anhui, China
| | - Sheng Xu
- The First Affiliated Hospital, Anhui University of Science and Technology, Anhui, China
| | - Mingming Zhang
- Department of Medical Immunology, School of Medicine, Anhui University of Science and Technology, Anhui, China
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China
- *Correspondence: Mingming Zhang,
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Yang M, Sun M, Zhang H. The Interaction Between Epigenetic Changes, EMT, and Exosomes in Predicting Metastasis of Colorectal Cancers (CRC). Front Oncol 2022; 12:879848. [PMID: 35712512 PMCID: PMC9197117 DOI: 10.3389/fonc.2022.879848] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 04/01/2022] [Indexed: 12/12/2022] Open
Abstract
Worldwide, colorectal cancer (CRC) ranks as the third most common malignancy, and the second most deadly with nearly one million attributable deaths in 2020. Metastatic disease is present in nearly 25% of newly diagnosed CRC, and despite advances in chemotherapy, less than 20% will remain alive at 5 years. Epigenetic change plays a key role in the epithelial-to-mesenchymal transition (EMT), which is a crucial phenotype for metastasis and mainly includes DNA methylation, non-coding RNAs (ncRNAs), and N6-methyladenosine (m6A) RNA, seemingly valuable biomarkers in CRCs. For ncRNAs, there exists a “molecular sponge effect” between long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). The detection of exosomes is a novel method in CRC monitoring, especially for predicting metastasis. There is a close relationship between exosomes and EMT in CRCs. This review summarizes the close relationship between epigenetic changes and EMT in CRCs and emphasizes the crucial function of exosomes in regulating the EMT process.
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Tang PCT, Zhang YY, Li JSF, Chan MKK, Chen J, Tang Y, Zhou Y, Zhang D, Leung KT, To KF, Tang SCW, Lan HY, Tang PMK. LncRNA-Dependent Mechanisms of Transforming Growth Factor-β: From Tissue Fibrosis to Cancer Progression. Noncoding RNA 2022; 8:ncrna8030036. [PMID: 35736633 PMCID: PMC9227532 DOI: 10.3390/ncrna8030036] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 05/19/2022] [Accepted: 05/21/2022] [Indexed: 11/16/2022] Open
Abstract
Transforming growth factor-β (TGF-β) is a crucial pathogenic mediator of inflammatory diseases. In tissue fibrosis, TGF-β regulates the pathogenic activity of infiltrated immunocytes and promotes extracellular matrix production via de novo myofibroblast generation and kidney cell activation. In cancer, TGF-β promotes cancer invasion and metastasis by enhancing the stemness and epithelial mesenchymal transition of cancer cells. However, TGF-β is highly pleiotropic in both tissue fibrosis and cancers, and thus, direct targeting of TGF-β may also block its protective anti-inflammatory and tumor-suppressive effects, resulting in undesirable outcomes. Increasing evidence suggests the involvement of long non-coding RNAs (lncRNAs) in TGF-β-driven tissue fibrosis and cancer progression with a high cell-type and disease specificity, serving as an ideal target for therapeutic development. In this review, the mechanism and translational potential of TGF-β-associated lncRNAs in tissue fibrosis and cancer will be discussed.
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Affiliation(s)
- Philip Chiu-Tsun Tang
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong 999077, China; (P.C.-T.T.); (J.S.-F.L.); (M.K.-K.C.); (K.-F.T.)
| | - Ying-Ying Zhang
- Department of Nephrology, Tongji University School of Medicine, Shanghai 200065, China;
| | - Jane Siu-Fan Li
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong 999077, China; (P.C.-T.T.); (J.S.-F.L.); (M.K.-K.C.); (K.-F.T.)
| | - Max Kam-Kwan Chan
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong 999077, China; (P.C.-T.T.); (J.S.-F.L.); (M.K.-K.C.); (K.-F.T.)
| | - Jiaoyi Chen
- Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong 999077, China; (J.C.); (S.C.-W.T.)
| | - Ying Tang
- Department of Nephrology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510080, China;
| | - Yiming Zhou
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China;
| | - Dongmei Zhang
- College of Pharmacy, Jinan University, Guangzhou 510632, China;
| | - Kam-Tong Leung
- Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong 999077, China;
| | - Ka-Fai To
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong 999077, China; (P.C.-T.T.); (J.S.-F.L.); (M.K.-K.C.); (K.-F.T.)
| | - Sydney Chi-Wai Tang
- Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong 999077, China; (J.C.); (S.C.-W.T.)
| | - Hui-Yao Lan
- Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China;
| | - Patrick Ming-Kuen Tang
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong 999077, China; (P.C.-T.T.); (J.S.-F.L.); (M.K.-K.C.); (K.-F.T.)
- Correspondence:
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22
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Pavlič A, Hauptman N, Boštjančič E, Zidar N. Long Non-Coding RNAs as Potential Regulators of EMT-Related Transcription Factors in Colorectal Cancer—A Systematic Review and Bioinformatics Analysis. Cancers (Basel) 2022; 14:cancers14092280. [PMID: 35565409 PMCID: PMC9105237 DOI: 10.3390/cancers14092280] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/29/2022] [Accepted: 04/30/2022] [Indexed: 12/15/2022] Open
Abstract
Simple Summary Emerging evidence highlights long non-coding RNAs as important regulators of epithelial–mesenchymal transition. Numerous studies have attempted to define their possible diagnostic, prognostic and therapeutic values in various human cancers. The aim of this review is to summarize long non-coding RNAs involved in the regulation of epithelial–mesenchymal transition in colorectal carcinoma. Additional candidate long non-coding RNAs are identified through a bioinformatics analysis. Abstract Epithelial–mesenchymal transition (EMT) plays a pivotal role in carcinogenesis, influencing cancer progression, metastases, stemness, immune evasion, metabolic reprogramming and therapeutic resistance. EMT in most carcinomas, including colorectal carcinoma (CRC), is only partial, and can be evidenced by identification of the underlying molecular drivers and their regulatory molecules. During EMT, cellular reprogramming is orchestrated by core EMT transcription factors (EMT-TFs), namely ZEB1/2, TWIST1/2, SNAI1 (SNAIL) and SNAI2 (SLUG). While microRNAs have been clearly defined as regulators of EMT, the role of long non-coding RNAs (lncRNAs) in EMT is poorly defined and controversial. Determining the role of lncRNAs in EMT remains a challenge, because they are involved in a number of cellular pathways and are operating through various mechanisms. Adding to the complexity, some lncRNAs have controversial functions across different tumor types, acting as EMT promotors in some tumors and as EMT suppressors in others. The aim of this review is to summarize the role of lncRNAs involved in the regulation of EMT-TFs in human CRC. Additional candidate lncRNAs were identified through a bioinformatics analysis.
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Fan B, Zhang Q, Wang N, Wang G. LncRNAs, the Molecules Involved in Communications With Colorectal Cancer Stem Cells. Front Oncol 2022; 12:811374. [PMID: 35155247 PMCID: PMC8829571 DOI: 10.3389/fonc.2022.811374] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 01/07/2022] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer stem cells (CRCSCs) can actively self-renew, as well as having multidirectional differentiation and tumor regeneration abilities. Because the high functional activities of CRCSCs are associated with low cure rates in patients with colorectal cancer, efforts have sought to determine the function and regulatory mechanisms of CRCSCs. To date, however, the potential regulatory mechanisms of CRCSCs remain incompletely understood. Many non-coding genes are involved in tumor invasion and spread through their regulation of CRCSCs, with long non-coding RNAs (lncRNAs) being important non-coding RNAs. LncRNAs may be involved in the colorectal cancer development and drug resistance through their regulation of CRCSCs. This review systematically evaluates the latest research on the ability of lncRNAs to regulate CRCSC signaling pathways and the involvement of these lncRNAs in colorectal cancer promotion and suppression. The regulatory network of lncRNAs in the CRCSC signaling pathway has been determined. Further analysis of the potential clinical applications of lncRNAs as novel clinical diagnostic and prognostic biomarkers and therapeutic targets for colorectal cancer may provide new ideas and protocols for the prevention and treatment of colorectal cancer.
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Affiliation(s)
- Boyang Fan
- Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Qian Zhang
- Department of Colorectal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
| | - Ning Wang
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China
| | - Guiyu Wang
- Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Hamidi AA, Khalili-Tanha G, Nasrpour Navaei Z, Moghbeli M. Long non-coding RNAs as the critical regulators of epithelial mesenchymal transition in colorectal tumor cells: an overview. Cancer Cell Int 2022; 22:71. [PMID: 35144601 PMCID: PMC8832734 DOI: 10.1186/s12935-022-02501-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Accepted: 01/30/2022] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer (CRC) is the second most common cause of cancer mortality and a major health challenge worldwide. Despite advances in therapeutic and diagnostic methods, there is still a poor prognosis in CRC patients. Tumor recurrence and metastasis are the main causes of high mortality rate in these patients, which are due to late diagnosis in advanced tumor stages. Epithelial-mesenchymal transition (EMT) is known to be the most important cause of CRC metastasis, during which tumor cells obtain metastasis ability by losing epithelial features and gaining mesenchymal features. Long non-coding RNAs (lncRNAs) are pivotal regulators of EMT process. Regarding the higher stability of lncRNAs compared with coding RNAs in body fluids, they can be used as non-invasive diagnostic markers for EMT process. In the present review, we summarized all of the lncRNAs involved in regulation of EMT process during CRC progression and metastasis. It was observed that lncRNAs mainly induced the EMT process in CRC cells by regulation of EMT-related transcription factors, Poly comb repressive complex (PRC), and also signaling pathways such as WNT, NOTCH, MAPK, and Hippo.
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Affiliation(s)
- Amir Abbas Hamidi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ghazaleh Khalili-Tanha
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Nasrpour Navaei
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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25
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Si L, Yang Z, Ding L, Zhang D. Regulatory effects of lncRNAs and miRNAs on the crosstalk between autophagy and EMT in cancer: a new era for cancer treatment. J Cancer Res Clin Oncol 2022; 148:547-564. [PMID: 35083552 DOI: 10.1007/s00432-021-03892-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 12/15/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Autophagy and EMT (epithelial-mesenchymal transition) are the two principal biological processes and ideal therapeutic targets during cancer development. Autophagy, a highly conserved process for degrading dysfunctional cellular components, plays a dual role in tumors depending on the tumor stage and tissue types. The EMT process is the transition differentiation from an epithelial cell to a mesenchymal-like cell and acquiring metastatic potential. There is evidence that the crosstalk between autophagy and EMT is complex in cancer. In recent years, more studies have shown that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in autophagy, EMT, and their crosstalk. Therefore, accurate understanding of the regulatory mechanisms of lncRNAs and miRNAs in autophagy, EMT and their interactions is crucial for the clinical management of cancers. METHODS An extensive literature search was conducted on the Google Scholar and PubMed databases. The keywords used for the search included: autophagy, EMT, crosstalk, lncRNAs, miRNAs, cancers, diagnostic biomarkers, and therapeutic targets. This search provided relevant articles published in peer-reviewed journals until 2021. Data from these various studies were extracted and used in this review. RESULTS The results showed that lncRNAs/miRNAs as tumor inhibitors or tumor inducers could regulate autophagy, EMT, and their interaction by regulating several molecular signaling pathways. The lncRNAs/miRNAs involved in autophagy and EMT processes could have potential uses in cancer diagnosis, prognosis, and therapy. CONCLUSION Such information could help find and develop lncRNAs/miRNAs based new tools for diagnosing, prognosis, and creating anti-cancer therapies.
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Affiliation(s)
- Lihui Si
- Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130000, China
| | - Zecheng Yang
- Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, 130000, China.
| | - Lu Ding
- Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, 130000, China
| | - Duoduo Zhang
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, 130000, Jilin Province, China
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26
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Emerging Role of LncRNAs in Autoimmune Lupus. Inflammation 2022; 45:937-948. [DOI: 10.1007/s10753-021-01607-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 11/11/2021] [Accepted: 12/05/2021] [Indexed: 12/13/2022]
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Potential Effects of Metformin on the Vitality, Invasion, and Migration of Human Vascular Smooth Muscle Cells via Downregulating lncRNA-ATB. DISEASE MARKERS 2022; 2022:7480199. [PMID: 35027983 PMCID: PMC8752240 DOI: 10.1155/2022/7480199] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/07/2021] [Accepted: 12/10/2021] [Indexed: 12/16/2022]
Abstract
Objective To elucidate the role of metformin in influencing VSMCs via the involvement of lncRNA-ATB. Methods qRT-PCR was conducted to detect serum levels of lncRNA-ATB and p53 in CHD patients (n = 50) and healthy subjects (n = 50). Correlation in serum levels of lncRNA-ATB and p53 in CHD patients was assessed by Pearson correlation test. ROC curves were depicted for analyzing the predictive potential of lncRNA-ATB in the occurrence of CHD. After metformin induction in VSMCs overexpressing lncRNA-ATB, relative levels of lncRNA-ATB and p53 were detected. Meanwhile, proliferative, migratory, and invasive abilities in VSMCs were, respectively, examined by CCK-8 and transwell assay. The interaction between lncRNA-ATB and p53 was tested by RIP. In addition, the coregulation of lncRNA-ATB and p53 in cell functions of VSMCs was finally determined. Results Increased serum level of lncRNA-ATB and decreased p53 level were detected in CHD patients than those of healthy subjects. LncRNA-ATB could interact with p53 and negatively regulate its level. In addition, lncRNA-ATB could serve as a potential biomarker for predicting the occurrence of CHD. The overexpression of lncRNA-ATB triggered viability, migratory, and invasive abilities in VSMCs, and the above trends were abolished by metformin induction. The overexpression of p53 partially abolished the promotive effects of lncRNA-ATB on proliferative, migratory, and invasive abilities in VSMCs. Conclusions Metformin induction inhibits proliferative, migratory, and invasive abilities in VSMCs by downregulating lncRNA-ATB, which may be related to p53 activation.
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Yue B, Cui R, Zheng R, Jin W, Song C, Bao T, Wang M, Yu F, Zhao E. Essential role of ALKBH5-mediated RNA demethylation modification in bile acid-induced gastric intestinal metaplasia. MOLECULAR THERAPY-NUCLEIC ACIDS 2021; 26:458-472. [PMID: 34631277 PMCID: PMC8479281 DOI: 10.1016/j.omtn.2021.08.019] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Accepted: 08/19/2021] [Indexed: 01/10/2023]
Abstract
Bile acid reflux and subsequent caudal-related homeobox 2 (CDX2) activation contribute to gastric intestinal metaplasia (IM), a precursor of gastric cancer; however, the mechanism underlying this phenomenon is unclear. Here, we demonstrate that alkylation repair homolog protein 5 (ALKBH5), a major RNA N6-adenosine demethylase, is required for bile acid-induced gastric IM. Mechanistically, we revealed the N6-methyladenosine (m6A) modification profile in gastric IM for the first time and identified ZNF333 as a novel m6A target of ALKBH5. ALKBH5 was shown to demethylate ZNF333 mRNA, leading to enhanced ZNF333 expression by abolishing m6A-YTHDF2-dependent mRNA degradation. In addition, ALKBH5 activated CDX2 and downstream intestinal markers by targeting the ZNF333/CYLD axis and activating NF-κB signaling. Reciprocally, p65, the key transcription factor of the canonical NF-κB pathway, enhanced the transcription activity of ALKBH5 in the nucleus, thus forming a positive feedforward circuit. Furthermore, ALKBH5 levels were positively correlated with ZNF333 and CDX2 levels in IM tissues, indicating significant clinical relevance. Collectively, our findings suggest that an m6A modification-associated positive feedforward loop between ALKBH5 and NF-κB signaling is involved in generating the IM phenotype of gastric epithelial cells. Targeting the ALKBH5/ZNF333/CYLD/CDX2 axis may be a useful therapeutic strategy for gastric IM in patients with bile regurgitation.
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Affiliation(s)
- Ben Yue
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
| | - Ran Cui
- Department of Hepatopancreatobiliary Surgery, Shanghai East Hospital, Tongji University School of Medicine, 1800 Yuntai Road, Shanghai 200120, China
| | - Ruizhe Zheng
- Department of Neurosurgery, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200336, China
| | - Weilin Jin
- Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China
| | - Chenlong Song
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, 85 Wujin Road, Shanghai 200080, China
| | - Tianshang Bao
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
| | - Ming Wang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
- Corresponding author: Ming Wang, PhD, Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
| | - Fengrong Yu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
- Corresponding author: Fengrong Yu, PhD, Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
| | - Enhao Zhao
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
- Corresponding author: Enhao Zhao, PhD, Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
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29
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Li Y, Wang L, Xu X, Sun H, Wu L. LncRNA HLA Complex Group 11 Knockdown Alleviates Cisplatin Resistance in Gastric Cancer by Targeting the miR-144-3p/UBE2D1 Axis. Cancer Manag Res 2021; 13:7543-7557. [PMID: 34629901 PMCID: PMC8493275 DOI: 10.2147/cmar.s329846] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/20/2021] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE Cisplatin (DDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). LncRNA noncoding RNA HLA complex group 11 (lncRNA HCG11) has been confirmed to promote GC progression. This study attempted to investigate the underlying molecular mechanism of HCG11 in DDP resistance of GC. METHODS qRT-PCR was performed to evaluate the expression of HCG11, microRNA-144-3p (miR-144-3p), and ubiquitin-conjugating enzyme E2 D1 (UBE2D1) in GC. The correlation between HCG11 and clinicopathological features of GC patients was assessed. DDP-resistant GC cells and their parental cells were cultured in different concentrations of DDP. The role of HCG11 for the viability and the half maximal inhibitory concentration (IC50) of DDP in DDP-resistant GC cells was determined by MTT assay. Then, the invasion of DDP-resistant GC cells was measured by transwell assay. Next, a dual-luciferase reporter assay was used to confirm the interactions among HCG11, miR-144-3p, and UBE2D1 in GC. RESULTS The expression of HCG11 and UBE2D1 was elevated in tumor tissues of GC patients, but miR-144-3p was declined. HCG11 expression was elevated in DDP-resistant GC patients and is strongly correlated with DDP sensitivity and World Health Organization grade in GC patients. HCG11 knockdown reduced the viability, IC50 of DDP, and invasion of DDP-resistant GC cells. Additionally, HCG11 targeted miR-144-3p and miR-144-3p further targeted UBE2D1. Feedback experiments indicated that low expression of miR-144-3p or overexpression of UBE2D1 mitigated the inhibitory effect of HCG11 depletion on DDP resistance of GC cells. CONCLUSION HCG11 knockdown attenuated DDP resistance of GC cells through via miR-144-3p/UBE2D1 axis, affording a novel therapeutic strategy for GC.
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Affiliation(s)
- Yu Li
- Department of Oncology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin City, Heilongjiang Province, 150040, People’s Republic of China
| | - Liqin Wang
- Nursing Teaching and Research Department, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin City, Heilongjiang Province, 150040, People’s Republic of China
| | - Xiaoyi Xu
- Department of Medical Laboratory, First Clinical Medical College, Mudanjiang Medical University, Mudanjiang City, Heilongjiang Province, 157011, People’s Republic of China
| | - Heng Sun
- Department of Oncology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin City, Heilongjiang Province, 150040, People’s Republic of China
| | - Leilei Wu
- Pharmacy Laboratory, College of Pharmacy, Mudanjiang Medical University, Mudanjiang City, Heilongjiang Province, 157011, People’s Republic of China
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30
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Asadi MR, Hassani M, Kiani S, Sabaie H, Moslehian MS, Kazemi M, Ghafouri-Fard S, Taheri M, Rezazadeh M. The Perspective of Dysregulated LncRNAs in Alzheimer's Disease: A Systematic Scoping Review. Front Aging Neurosci 2021; 13:709568. [PMID: 34621163 PMCID: PMC8490871 DOI: 10.3389/fnagi.2021.709568] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 08/12/2021] [Indexed: 12/22/2022] Open
Abstract
LncRNAs act as part of non-coding RNAs at high levels of complex and stimulatory configurations in basic molecular mechanisms. Their extensive regulatory activity in the CNS continues on a small scale, from the functions of synapses to large-scale neurodevelopment and cognitive functions, aging, and can be seen in both health and disease situations. One of the vast consequences of the pathological role of dysregulated lncRNAs in the CNS due to their role in a network of regulatory pathways can be manifested in Alzheimer's as a neurodegenerative disease. The disease is characterized by two main hallmarks: amyloid plaques due to the accumulation of β-amyloid components and neurofibrillary tangles (NFT) resulting from the accumulation of phosphorylated tau. Numerous studies in humans, animal models, and various cell lines have revealed the role of lncRNAs in the pathogenesis of Alzheimer's disease. This scoping review was performed with a six-step strategy and based on the Prisma guideline by systematically searching the publications of seven databases. Out of 1,591 records, 69 articles were utterly aligned with the specified inclusion criteria and were summarized in the relevant table. Most of the studies were devoted to BACE1-AS, NEAT1, MALAT1, and SNHG1 lncRNAs, respectively, and about one-third of the studies investigated a unique lncRNA. About 56% of the studies reported up-regulation, and 7% reported down-regulation of lncRNAs expressions. Overall, this study was conducted to investigate the association between lncRNAs and Alzheimer's disease to make a reputable source for further studies and find more molecular therapeutic goals for this disease.
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Affiliation(s)
- Mohammad Reza Asadi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Hassani
- Student Research Committee, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Shiva Kiani
- Department of Molecular Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hani Sabaie
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Marziyeh Sadat Moslehian
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Kazemi
- Department of Social Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Rezazadeh
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Circulating Long Non-Coding RNAs as Novel Potential Biomarkers for Osteogenic Sarcoma. Cancers (Basel) 2021; 13:cancers13164214. [PMID: 34439367 PMCID: PMC8392488 DOI: 10.3390/cancers13164214] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 08/09/2021] [Accepted: 08/11/2021] [Indexed: 12/11/2022] Open
Abstract
Circulating cell-free nucleic acids recently became attractive targets to develop non-invasive diagnostic tools for cancer detection. Along with DNA and mRNAs, transcripts lacking coding potential (non-coding RNAs, ncRNAs) directly involved in the process of tumor pathogenesis have been recently detected in liquid biopsies. Interestingly, circulating ncRNAs exhibit specific expression patterns associated with cancer and suggest their role as novel biomarkers. However, the potential of circulating long ncRNAs (c-lncRNAs) to be markers in osteosarcoma (OS) is still elusive. In this study we performed a systematic review to identify thirteen c-lncRNAs whose altered expression in blood associate with OS. We herein discuss the potential impact that these c-lncRNAs may have on clinical decision-making in the management of OS. Overall, we aimed to provide novel insights that can contribute to the development of future precision medicine in oncology.
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32
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Liu F, Song ZM, Wang XD, Du SY, Peng N, Zhou JR, Zhang MG. Long Non-coding RNA Signature for Liver Metastasis of Colorectal Cancers. Front Cell Dev Biol 2021; 9:707115. [PMID: 34307387 PMCID: PMC8297503 DOI: 10.3389/fcell.2021.707115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 06/14/2021] [Indexed: 12/30/2022] Open
Abstract
Colorectal cancer ranks within the top three cancers both in terms of incidence as well as deaths. Metastasis is often the major cause of mortality and liver is the primary and most common site to which colorectal cancers metastasize. We tested the prognostic ability of a long non-coding RNA (lncRNA) signature in liver metastatic colorectal cancers. We first evaluated expression levels of several lncRNAs in eight excised liver metastases from primary colorectal cancers and found significantly upregulated lncRNAs HOTAIR and MALAT1 along with significantly downregulated LOC285194. We further compared the expression levels of HOTAIR, MALAT1 and LOC285194 in primary colorectal tumors at the time of initial diagnosis and correlated them with disease progression and liver metastasis. HOTAIR and MALAT1 were significantly upregulated and LOC285194 was significantly downregulated in twelve patients who were diagnosed with liver metastasis within 5 years of initial diagnosis, compared to the five patients with no metastasis. A positive signature comprising of high HOTAIR/MALAT1 and low LOC285194 also correlated with progression to higher grade tumors. Thus, the lncRNA signature comprising of high HOTAIR/MALAT1 and low LOC285194 could be a prognostic signature for liver metastasis as well as overall poor survival.
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Affiliation(s)
- Fang Liu
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Zhen-Mei Song
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Xiao-Di Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Shi-Yu Du
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Na Peng
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Jing-Rui Zhou
- Department of Gastroenterology, Shan GU Hospital, Handan, China
| | - Ming-Gang Zhang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
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Algaber A, Madhi R, Hawez A, Rönnow CF, Rahman M. Targeting FHL2-E-cadherin axis by miR-340-5p attenuates colon cancer cell migration and invasion. Oncol Lett 2021; 22:637. [PMID: 34295384 PMCID: PMC8273858 DOI: 10.3892/ol.2021.12898] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 03/25/2021] [Indexed: 01/04/2023] Open
Abstract
Convincing data has suggested that four and a half LIM domain 2 protein (FHL2) serves a key function in cancer cell metastasis and that microRNA (miR)-340-5p can regulate cancer cell migration. The current study hypothesized that targeting FHL2 expression by miR-340-5p in colon cancer may attenuate colon cancer cell migration and invasion. FHL2 expression was therefore assessed in colon cancer microarray datasets using Qlucore omics explorer as well as in HT-29 and AZ-97 colon cancer cell lines via reverse transcription-quantitative PCR (RT-qPCR). Colon cancer cell migration and invasion were evaluated in the presence of miR-340-5p mimic, mimic control or mimic with a target site blocker. Confocal microscopy and RT-qPCR were subsequently performed to assess FHL2, E-cadherin (E-cad) protein and mRNA expression in colon cancer cells. Microarray dataset analysis revealed that FHL2 expression was lower in primary colon cancer cells compared with normal colonic mucosa. It was revealed that the expression of miR-340-5p and FHL2 were inversely related in serum-grown and low-serum conditions in HT-29 and AZ-97 cells. Short-time serum exposure to low-serum grown cells induced FHL2 expression. Transfection of HT-29 cells with miR-340-5p mimic not only decreased serum-induced expression of FHL2 but also decreased cancer cell migration and invasion. Bioinformatics analysis revealed that FHL2 mRNA had one putative binding site for miR-340-5p at the 3-untranslated region. Blocking of the target site using a specific blocker reverted miR-340-5p mimic-induced inhibition of FHL2 expression and cancer cell migration and invasion. Confocal microscopy confirmed that the reduction of FHL2 expression by miR-340-5p mimic also reversed serum-induced E-cad disruption and that the target site blocker abrogated the effect of miR-340-5p. The current results suggested that miR-340-5p could be used to antagonize colon cancer cell metastasis by targeting the FHL2-E-cad axis.
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Affiliation(s)
- Anwar Algaber
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, 214 28 Malmö, Sweden
| | - Raed Madhi
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, 214 28 Malmö, Sweden.,Department of Biology, College of Science, University of Misan, Maysan 62001, Iraq
| | - Avin Hawez
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, 214 28 Malmö, Sweden
| | - Carl-Fredrik Rönnow
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, 214 28 Malmö, Sweden
| | - Milladur Rahman
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, 214 28 Malmö, Sweden
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Zhang S, Li J, Gao H, Tong Y, Li P, Wang Y, Du L, Wang C. lncRNA Profiles Enable Prognosis Prediction and Subtyping for Esophageal Squamous Cell Carcinoma. Front Cell Dev Biol 2021; 9:656554. [PMID: 34127945 PMCID: PMC8196240 DOI: 10.3389/fcell.2021.656554] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 04/08/2021] [Indexed: 12/24/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) have emerged as useful prognostic markers in many tumors. In this study, we investigated the potential application of lncRNA markers for the prognostic prediction of esophageal squamous cell carcinoma (ESCC). We identified ESCC-associated lncRNAs by comparing ESCC tissues with normal tissues. Subsequently, Kaplan–Meier (KM) method in combination with the univariate Cox proportional hazards regression (UniCox) method was used to screen prognostic lncRNAs. By combining the differential and prognostic lncRNAs, we developed a prognostic model using cox stepwise regression analysis. The obtained prognostic prediction model could effectively predict the 3- and 5-year prognosis and survival of ESCC patients by time-dependent receiver operating characteristic (ROC) curves (area under curve = 0.87 and 0.89, respectively). Besides, a lncRNA-based classification of ESCC was generated using k-mean clustering method and we obtained two clusters of ESCC patients with association with race and Barrett’s esophagus (BE) (both P < 0.001). Finally, we found that lncRNA AC007128.1 was upregulated in both ESCC cells and tissues and associated with poor prognosis of ESCC patients. Furthermore, AC007128.1 could promote epithelial-mesenchymal transition (EMT) of ESCC cells by increasing the activation of MAPK/ERK and MAPK/p38 signaling pathways. Collectively, our findings indicated the potentials of lncRNA markers in the prognosis, molecular subtyping, and EMT of ESCC.
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Affiliation(s)
- Shujun Zhang
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Juan Li
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Huiru Gao
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yao Tong
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Peilong Li
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yunshan Wang
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lutao Du
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, China.,Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, China
| | - Chuanxin Wang
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, China.,Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, China
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35
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Decoding LncRNAs. Cancers (Basel) 2021; 13:cancers13112643. [PMID: 34072257 PMCID: PMC8199187 DOI: 10.3390/cancers13112643] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 05/23/2021] [Accepted: 05/25/2021] [Indexed: 02/07/2023] Open
Abstract
Non-coding RNAs (ncRNAs) have been considered as unimportant additions to the transcriptome. Yet, in light of numerous studies, it has become clear that ncRNAs play important roles in development, health and disease. Long-ignored, long non-coding RNAs (lncRNAs), ncRNAs made of more than 200 nucleotides have gained attention due to their involvement as drivers or suppressors of a myriad of tumours. The detailed understanding of some of their functions, structures and interactomes has been the result of interdisciplinary efforts, as in many cases, new methods need to be created or adapted to characterise these molecules. Unlike most reviews on lncRNAs, we summarize the achievements on lncRNA studies by taking into consideration the approaches for identification of lncRNA functions, interactomes, and structural arrangements. We also provide information about the recent data on the involvement of lncRNAs in diseases and present applications of these molecules, especially in medicine.
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Kumari A, Shonibare Z, Monavarian M, Arend RC, Lee NY, Inman GJ, Mythreye K. TGFβ signaling networks in ovarian cancer progression and plasticity. Clin Exp Metastasis 2021; 38:139-161. [PMID: 33590419 PMCID: PMC7987693 DOI: 10.1007/s10585-021-10077-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 02/03/2021] [Indexed: 02/06/2023]
Abstract
Epithelial ovarian cancer (EOC) is a leading cause of cancer-related death in women. Late-stage diagnosis with significant tumor burden, accompanied by recurrence and chemotherapy resistance, contributes to this poor prognosis. These morbidities are known to be tied to events associated with epithelial-mesenchymal transition (EMT) in cancer. During EMT, localized tumor cells alter their polarity, cell-cell junctions, cell-matrix interactions, acquire motility and invasiveness and an exaggerated potential for metastatic spread. Key triggers for EMT include the Transforming Growth Factor-β (TGFβ) family of growth factors which are actively produced by a wide array of cell types within a specific tumor and metastatic environment. Although TGFβ can act as either a tumor suppressor or promoter in cancer, TGFβ exhibits its pro-tumorigenic functions at least in part via EMT. TGFβ regulates EMT both at the transcriptional and post-transcriptional levels as outlined here. Despite recent advances in TGFβ based therapeutics, limited progress has been seen for ovarian cancers that are in much need of new therapeutic strategies. Here, we summarize and discuss several recent insights into the underlying signaling mechanisms of the TGFβ isoforms in EMT in the unique metastatic environment of EOCs and the current therapeutic interventions that may be relevant.
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Affiliation(s)
- Asha Kumari
- Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, WTI 320B, 1824 Sixth Avenue South, Birmingham, AL, 35294, USA
| | - Zainab Shonibare
- Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, WTI 320B, 1824 Sixth Avenue South, Birmingham, AL, 35294, USA
| | - Mehri Monavarian
- Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, WTI 320B, 1824 Sixth Avenue South, Birmingham, AL, 35294, USA
| | - Rebecca C Arend
- Department of Obstetrics and Gynecology-Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA
| | - Nam Y Lee
- Division of Pharmacology, Chemistry and Biochemistry, College of Medicine, University of Arizona, Tucson, AZ, 85721, USA
| | - Gareth J Inman
- Cancer Research UK Beatson Institute and Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Karthikeyan Mythreye
- Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, WTI 320B, 1824 Sixth Avenue South, Birmingham, AL, 35294, USA.
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Cheng T, Huang S. Roles of Non-Coding RNAs in Cervical Cancer Metastasis. Front Oncol 2021; 11:646192. [PMID: 33777808 PMCID: PMC7990873 DOI: 10.3389/fonc.2021.646192] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 02/03/2021] [Indexed: 12/24/2022] Open
Abstract
Metastasis remains to be a huge challenge in cancer therapy. The mechanism underlying cervical cancer metastasis is not well understood and needs to be elucidated. Recent studies have highlighted the diverse roles of non-coding RNAs in cancer progression and metastasis. Increasing numbers of miRNAs, lncRNAs and circRNAs are found to be dysregulated in cervical cancer, associated with metastasis. They have been shown to regulate metastasis through regulating metastasis-related genes, epithelial-mesenchymal transition, signaling pathways and interactions with tumor microenvironment. Moreover, miRNAs can interact with lncRNAs and circRNAs respectively during this complex process. Herein, we review literatures up to date involving non-coding RNAs in cervical cancer metastasis, mainly focus on the underlying mechanisms and highlight the interaction network between miRNAs and lncRNAs, as well as circRNAs. Finally, we discuss the therapeutic prospects.
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Affiliation(s)
- Tanchun Cheng
- Department of Obstetrics and Gynecology, Affiliated Haikou Hospital, Xiangya Medical College of Central South University, Haikou, China
| | - Shouguo Huang
- Department of Obstetrics and Gynecology, Affiliated Haikou Hospital, Xiangya Medical College of Central South University, Haikou, China
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Liao Z, Nie H, Wang Y, Luo J, Zhou J, Ou C. The Emerging Landscape of Long Non-Coding RNAs in Colorectal Cancer Metastasis. Front Oncol 2021; 11:641343. [PMID: 33718238 PMCID: PMC7947863 DOI: 10.3389/fonc.2021.641343] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 01/29/2021] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common gastrointestinal cancers, with extremely high rates of morbidity and mortality. The main cause of death in CRC is distant metastasis; it affects patient prognosis and survival and is one of the key challenges in the treatment of CRC. Long non-coding RNAs (lncRNAs) are a group of non-coding RNA molecules with more than 200 nucleotides. Abnormal lncRNA expression is closely related to the occurrence and progression of several diseases, including cancer. Recent studies have shown that numerous lncRNAs play pivotal roles in the CRC metastasis, and reversing the expression of these lncRNAs through artificial means can reduce the malignant phenotype of metastatic CRC to some extent. This review summarizes the major mechanisms of lncRNAs in CRC metastasis and proposes lncRNAs as potential therapeutic targets for CRC and molecular markers for early diagnosis.
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Affiliation(s)
- Zhiming Liao
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Hui Nie
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Yutong Wang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Jingjing Luo
- Teaching and Research Room of Biochemistry and Molecular Biology, Medical School of Hunan University of Traditional Chinese Medicine, Changsha, China
| | - Jianhua Zhou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Chunlin Ou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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Abstract
Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2021;10(2):122-133.
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Affiliation(s)
- Chao Peng He
- Department of Orthopedics, The Second Affiliated Hospital, Hunan Normal University, Hunan, China
| | - Xin Chen Jiang
- Department of Orthopedics, The Second Affiliated Hospital, Hunan Normal University, Hunan, China
| | - Cheng Chen
- Department of Orthopedics, The Second Affiliated Hospital, Hunan Normal University, Hunan, China
| | - Hai Bin Zhang
- Department of Orthopedics, The Xiangya Hospital of Central South University Changsha, Hunan, China
| | - Wen Dong Cao
- Department of Orthopedics, The Second Affiliated Hospital, Hunan Normal University, Hunan, China
| | - Qi Wu
- Department of Orthopedics, The Second Affiliated Hospital, Hunan Normal University, Hunan, China
| | - Chi Ma
- Department of Orthopedics, The First Affiliated Hospital (People’s Hospital of Xiangxi Autonomous Prefecture), Jishou University, Jishou, China
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Jiang A, Liu N, Bai S, Wang J, Gao H, Zheng X, Fu X, Ren M, Zhang X, Tian T, Ruan Z, Liang X, Yao Y. Identification and validation of an autophagy-related long non-coding RNA signature as a prognostic biomarker for patients with lung adenocarcinoma. J Thorac Dis 2021; 13:720-734. [PMID: 33717544 PMCID: PMC7947511 DOI: 10.21037/jtd-20-2803] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Background Lung adenocarcinoma (LUAD) is the most predominant pathological subtype of lung cancer, accounting for 40–70% of all lung cancer cases. Although significant improvements have been made in the screening, diagnosis, and precise management in recent years, the prognosis of LUAD remains bleak. This study aimed to investigate the prognostic significance of autophagy-related long non-coding RNAs (lncRNAs) and construct an autophagy-related lncRNA prognostic model in LUAD. Methods The gene expression data of LUAD patients were obtained from The Cancer Genome Atlas (TCGA) database. All autophagy-related genes were downloaded from the Human Autophagy Database (HADb). Spearman’s correlation test was exploited to identify potential autophagy-related lncRNAs. The multivariate Cox regression analysis was used to construct the prognostic signature, which divided LUAD patients into high-risk and low-risk groups. Subsequently, the receiver operating characteristic (ROC) curves were generated to assess the predictive ability of this prognostic model for overall survival (OS) in these individuals. Then, the Gene set enrichment analysis (GSEA) was conducted to execute pathway enrichment analysis. Finally, a multidimensional validation was exploited to verify our findings. Results A total of 1,144 autophagy-related lncRNAs were identified to construct the co-expression network via Spearman’s correlation test (|R2| >0.4 and P≤0.001). Ultimately, a 16 autophagy-related lncRNAs prognostic model was constructed, and the area under the ROC curve (AUC) was 0.775. The results of GSEA enrichment analysis showed that the genes in the high-risk group were mainly enriched in cell cycle and p53 signaling pathways. The results of the multidimensional database validation indicated that the expression level of BIRC5 was significantly correlated with the expression level of TMPO-AS1. Furthermore, both TMPO-AS1 and BIRC5 had a higher expression level in LUAD samples. LUAD patients with high expression levels of TMPO-AS1 and BIRC5 were correlated with advanced disease stage and poor OS. Conclusions In summary, our results suggested that the prognostic signature of the 16 autophagy-related lncRNAs has significant prognostic value for LUAD patients. Furthermore, TMPO-AS1 and BIRC5 are potential predictors and therapeutic targets in these individuals.
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Affiliation(s)
- Aimin Jiang
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Na Liu
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shuheng Bai
- Department of Radiotherapy Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jingjing Wang
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Huan Gao
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaoqiang Zheng
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiao Fu
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Mengdi Ren
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaoni Zhang
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Tao Tian
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhiping Ruan
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xuan Liang
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yu Yao
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Zhang ZH, Wang LM. Effects of lncRNA LINC01224/miR-513b-5p on proliferation, migration, and invasion of colon cancer SW1116 cells. Shijie Huaren Xiaohua Zazhi 2021; 29:7-14. [DOI: 10.11569/wcjd.v29.i1.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The incidence and mortality of colon cancer in China are increasing year by year. At present, the pathogenesis of colon cancer has not been elucidated. Long non-coding RNAs (lncRNAs) play an important regulatory role in the occurrence of colon cancer and other tumors mainly by competitively binding microRNAs. It is known that the lncRNA LINC01224 may play an oncogenic role in tumors, but the mechanism of LINC01224 in the development and progression of colon cancer has not been elucidated.
AIM To explore the effects of lncRNA LINC01224/miR-513b-5p on the proliferation, migration, and invasion of colon cancer SW1116 cells and the possible mechanism involved.
METHODS qRT-PCR was used to detect the expression of LINC01224 and miR-513b-5p in colon cancer and tumor adjacent tissues. si-NC, si-LINC01224, and si-LINC01224, as well as anti-miR-NC, si-LINC01224, and anti-miR-513b-5p were transfected into human colon cancer SW1116 cells. qRT-PCR was used to detect the expression of LINC01224 and miR-513b-5p in SW1116 cells. MTT assay was used to detect the cell survival rate. Flow cytometry was used to detect the cell cycle. Transwell assay was used to detect cell migration and invasion. The dual luciferase reporter assay was used to detect the targeting relationship between LINC01224 and miR-513b-5p. Western blot method was used to detect the expression of E-cadherin and N-cadherin proteins.
RESULTS Compared with adjacent tissues, the expression level of LINC01224 in colon cancer tissues was increased (P < 0.05), and the expression level of miR-513b-5p was decreased (P < 0.05). Compared with the si-NC group, the survival rate of cells in the si-LINC01224 group was reduced (P < 0.05), the proportion of cells in the G0-G1 phase was increased (P < 0.05), the proportion of cells in the S phase was reduced (P < 0.05), the numbers of migrating and invasive cells were decreased (P < 0.05), the protein level of E-cadherin was increased (P < 0.05), and the protein level of N-cadherin was decreased (P < 0.05). The dual luciferase reporter assay confirmed that LINC01224 could target miR-513b-5p. Compared with the si-LINC01224 + anti-miR-NC group, the cell survival rate of cells in the si-LINC01224 + anti-miR-513b-5p group was increased (P < 0.05), the proportion of cells in the G0-G1 phase was decreased (P < 0.05), the proportion of cells was increased (P < 0.05), the numbers of migrating and invasive cells were increased (P < 0.05), the protein level of E-cadherin was decreased (P < 0.05), and the protein level of N-cadherin was increased (P < 0.05).
CONCLUSION Interfering with the expression of LINC01224 reduces the proliferation, migration, and invasion of colon cancer cells by up-regulating miR-513b-5p, and induces cell cycle arrest in G0-G1 phase.
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Affiliation(s)
- Zhao-Hui Zhang
- Department of Hepatopancreatobiliary Surgery, Jinhua Central Hospital, Jinhua 321000, Zhejiang Province, China
| | - Li-Min Wang
- Department of Hepatopan-creatobiliary Surgery, Jinhua Central Hospital, Jinhua 321000, Zhejiang Province, China
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The potential of long noncoding RNAs for precision medicine in human cancer. Cancer Lett 2020; 501:12-19. [PMID: 33359450 DOI: 10.1016/j.canlet.2020.11.040] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 11/13/2020] [Accepted: 11/26/2020] [Indexed: 12/20/2022]
Abstract
Precision medicine promises to better classify patients by individual clinical and biological biomarkers, which may provide an accurate assessment of disease risk, diagnosis, prognosis and treatment response. Cancer frequently displays substantial inter-tumor and intra-tumor heterogeneity and hence oncology is well suited for application of precision approaches. Recent studies have demonstrated that dysregulated lncRNAs play pivotal roles in tumor heterogeneity. In this review, attention is focused on the potential applications of lncRNAs as biomarker candidates for cancer risk evaluation, detection, surveillance and prognosis. LncRNAs are often stable in clinical samples and easily detected. The functional implications and therapeutic potential of targeting lncRNAs in human cancer are further discussed. Finally, existing deficiencies and future perspectives in translating fundamental lncRNA knowledge into clinical practice are highlighted.
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Chen XJ, An N. Long noncoding RNA ATB promotes ovarian cancer tumorigenesis by mediating histone H3 lysine 27 trimethylation through binding to EZH2. J Cell Mol Med 2020; 25:37-46. [PMID: 33336896 PMCID: PMC7810921 DOI: 10.1111/jcmm.15329] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 04/02/2020] [Accepted: 04/04/2020] [Indexed: 12/26/2022] Open
Abstract
Ovarian cancer (OC) remains one of the most lethal gynecological malignancies. The unfavourable prognosis is mainly due to the lack of early‐stage diagnosis, drug resistance and recurrence. Therefore, it needs to investigate the mechanism of OC tumorigenesis and identify effective biomarkers for the clinical diagnosis. It is reported that long noncoding RNAs (lncRNAs) play important roles during the tumorigenesis of OC. Therefore, the present study aimed to study the role and clinical significance of LncRNAs ATB (lnc‐ATB) in the development and progression of OC. In our research, lnc‐ATB expression in OC tissues was elevated compared with adjacent normal tissues and high expression of lnc‐ATB was associated with poor outcomes of OC patients. The silencing of lnc‐ATB blocked cell proliferation, invasion and migration in SKOV3 and A2780 cells. RNA immunoprecipitation and RNA pull‐down results showed that lnc‐ATB positively regulated the expression of EZH2 via directly interacting with EZH2. Besides, the overexpression of EZH2 partly rescued lnc‐ATB silencing‐inducing inhibition of cell proliferation, invasion and migration. Chromatin immunoprecipitation assay results demonstrated that the silencing of lnc‐ATB reduced the occupancy of caudal‐related homeobox protein 1, Forkhead box C1, Large tumour suppressor kinase 2, cadherin‐1 and disabled homolog 2 interacting protein promoters on EZH2 and H3K27me3. These data revealed the oncogenic of lnc‐ATB and provided a novel biomarker for OC diagnosis. Furthermore, these findings indicated the mechanism of lnc‐ATB functioning in the progression of OC, which provided a new target for OC therapy.
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Affiliation(s)
- Xue-Juan Chen
- Department of Gynecology, Shengli Oilfield Central Hospital, Dongying, Shandong, China
| | - Na An
- Department of Gynecology, Shengli Oilfield Central Hospital, Dongying, Shandong, China
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Liu X, Wang C. Long non-coding RNA ATB is associated with metastases and promotes cell invasion in colorectal cancer via sponging miR-141-3p. Exp Ther Med 2020; 20:261. [PMID: 33199986 PMCID: PMC7664613 DOI: 10.3892/etm.2020.9391] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 08/21/2020] [Indexed: 12/15/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) serve crucial roles in cancer development and progression. lncRNA-activated by transforming growth factor-β (lncRNA-ATB) mediates cell proliferation. However, the association between lncRNA-ATB and human colorectal cancer (CRC) is not completely understood. Therefore, the present study aimed to investigate the role of lncRNA-ATB in CRC, as well as the underlying mechanism. 50 pairs of tumor tissues and adjacent normal tissues from patients with primary CRC were collected. The expression of lncRNA-ATB and microRNA (miR)-141-3p in CRC tissues, adjacent normal tissues and cell lines was detected using reverse transcription-quantitative PCR. CCK-8, colony formation, Transwell, western blot, dual luciferase reporter gene, RNA immunoprecipitation and immunohistochemistry staining assays were conducted to assess the biological function of lncRNA-ATB and miR-141-3p in CRC progression. lncRNA-ATB was upregulated in CRC tissues and cell lines compared with healthy tissues and cells, respectively. Moreover, high expression of lncRNA-ATB was significantly associated with advanced TNM stage and metastasis in CRC. In addition, the results indicated that lncRNA-ATB expression predicted the prognosis and overall survival of patients with CRC. Compared with small interfering RNA-negative control, lncRNA-ATB knockdown inhibited CRC cell proliferation, migration and invasion, whereas, compared with vector, lncRNA-ATB overexpression promoted CRC cell proliferation, migration and invasion. Furthermore, the in vivo experiment suggested that lncRNA-ATB knockdown inhibited tumor growth. The results also indicated that lncRNA-ATB may contribute to CRC progression via binding to tumor suppressor microRNA-141-3p. Collectively, the present study suggested a crucial role of lncRNA-ATB in CRC tumorigenesis, suggesting that lncRNA-ATB may serve as an important marker for the diagnosis and development of CRC.
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Affiliation(s)
- Xianming Liu
- Department of Gastrointestinal Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
| | - Cunchuan Wang
- Department of Gastrointestinal Surgery, Guangzhou Overseas Chinese Hospital, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China
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Chen S, Shen X. Long noncoding RNAs: functions and mechanisms in colon cancer. Mol Cancer 2020; 19:167. [PMID: 33246471 PMCID: PMC7697375 DOI: 10.1186/s12943-020-01287-2] [Citation(s) in RCA: 195] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 11/20/2020] [Indexed: 12/28/2022] Open
Abstract
Evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in the carcinogenesis and progression of a wide variety of human malignancies including colon cancer. In this review, we describe the functions and mechanisms of lncRNAs involved in colon oncogenesis, such as HOTAIR, PVT1, H19, MALAT1, SNHG1, SNHG7, SNHG15, TUG1, XIST, ROR and ZEB1-AS1. We summarize the roles of lncRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in colon cancer. In addition, we briefly highlight the functions of circRNAs in colon tumorigenesis and progression, including circPPP1R12A, circPIP5K1A, circCTIC1, circ_0001313, circRNA_104916 and circRNA-ACAP2. This review provides the rationale for anticancer therapy via modulation of lncRNAs and circular RNAs (circRNAs) in colon carcinoma.
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Affiliation(s)
- Sian Chen
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, No 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China
| | - Xian Shen
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, No 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China.
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Liu R, Zhao W, Wang H, Wang J. Long Noncoding RNA LINC01207 Promotes Colon Cancer Cell Proliferation and Invasion by Regulating miR-3125/TRIM22 Axis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:1216325. [PMID: 33299853 PMCID: PMC7704133 DOI: 10.1155/2020/1216325] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 10/12/2020] [Accepted: 10/29/2020] [Indexed: 12/03/2022]
Abstract
Increasing study has validated that long noncoding RNAs (lncRNAs) are involved in the growth and metastasis of colon cancer. LINC01207 has been reported to play vital roles in certain types of cancer, while the precise function of LINC01207 in the progression of colon cancer remains unclear. The objective of this study was to investigate the effect of LINC01207 on the growth and metastasis of colon cancer cells and to explore the underlying mechanism. We found that the expression of LINC01207 was significantly upregulated in colon adenocarcinoma tissues compared with normal tissues by the GEPIA database. Notably, silencing of LINC01207 significantly suppressed the proliferation, migration, and invasion abilities of SW480 and HT-29 cells. Mechanistically, our data demonstrated that LINC01207 could sponge miR-3125 in colon cancer cells. Moreover, miR-3125 could directly target TRIM22 and negatively regulate its expression. Rescue assays revealed that miR-3125 inhibitor or TRIM22 overexpression significantly reversed the repressive role of LINC01207 knockdown in colon cancer cell proliferation and invasion. In conclusion, LINC01207 exerts an oncogenic role in the progression of colon cancer by absorbing miR-3125 to modulating TRIM22 expression.
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Affiliation(s)
- Ronghong Liu
- Department of Nutrition Section, North China Petroleum Bureau General Hospital, Renqiu 062552, China
| | - Wenzeng Zhao
- Department of General Surgery, North China Petroleum Bureau General Hospital, Renqiu 062552, China
| | - Haigang Wang
- Department of General Surgery, North China Petroleum Bureau General Hospital, Renqiu 062552, China
| | - Jianbing Wang
- Department of Cardiovascular Medicine, North China Petroleum Bureau General Hospital, Renqiu 062552, China
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Yang F, Liu C, Zhao G, Ge L, Song Y, Chen Z, Liu Z, Hong K, Ma L. Long non-coding RNA LINC01234 regulates proliferation, migration and invasion via HIF-2α pathways in clear cell renal cell carcinoma cells. PeerJ 2020; 8:e10149. [PMID: 33088626 PMCID: PMC7568479 DOI: 10.7717/peerj.10149] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 09/21/2020] [Indexed: 12/21/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) have been proved to have an important role in different malignancies including clear cell renal cell carcinoma (ccRCC). However, their role in disease progression is still not clear. The objective of the study was to identify lncRNA-based prognostic biomarkers and further to investigate the role of one lncRNA LINC01234 in progression of ccRCC cells. We found that six adverse prognostic lncRNA biomarkers including LINC01234 were identified in ccRCC patients by bioinformatic analysis using The Cancer Genome Atlas database. LINC01234 knockdown impaired cell proliferation, migration and invasion in vitro as compared to negative control. Furthermore, the epithelial-mesenchymal transition was inhibited after LINC01234 knockdown. Additionally, LINC01234 knockdown impaired hypoxia-inducible factor-2a (HIF-2α) pathways, including a suppression of the expression of HIF-2α, vascular endothelial growth factor A, epidermal growth factor receptor, c-Myc, Cyclin D1 and MET. Together, these datas showed that LINC01234 was likely to regulate the progression of ccRCC by HIF-2α pathways, and LINC01234 was both a promising prognostic biomarker and a potential therapeutic target for ccRCC.
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Affiliation(s)
- Feilong Yang
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Cheng Liu
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Guojiang Zhao
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Liyuan Ge
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Yimeng Song
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Zhigang Chen
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Zhuo Liu
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Kai Hong
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Lulin Ma
- Department of Urology, Peking University Third Hospital, Beijing, China
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Jin LP, Liu T, Meng FQ, Tai JD. Prognosis prediction model based on competing endogenous RNAs for recurrence of colon adenocarcinoma. BMC Cancer 2020; 20:968. [PMID: 33028275 PMCID: PMC7541229 DOI: 10.1186/s12885-020-07163-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 07/10/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Colon adenocarcinoma (COAD) patients who develop recurrence have poor prognosis. Our study aimed to establish effective prognosis prediction model based on competing endogenous RNAs (ceRNAs) for recurrence of COAD. METHODS COAD expression profilings downloaded from The Cancer Genome Atlas (TCGA) were used as training dataset, and expression profilings of GSE29623 retrieved from Gene Expression Omnibus (GEO) were set as validation dataset. Differentially expressed RNAs (DERs) between non-recurrent and recurrent specimens in training dataset were screened, and optimum prognostic signature DERs were revealed to establish prognostic score (PS) model. Kaplan-Meier survival analysis was conducted for PS model, and GEO dataset was used for validation. Prognosis prediction efficiencies were evaluated by area under curve (AUC) and C-index. Meanwhile, ceRNA regulatory network was constructed by using signature mRNAs, lncRNAs and miRNAs. RESULTS We identified 562 DERs including 42 lncRNAs, 36 miRNAs, and 484 mRNAs. PS prediction model, consisting of 17 optimum prognostic signature DERs, showed that high risk group had significantly poorer prognosis (5-year AUC = 0.951, C-index = 0.788), which also validated in GSE29623. Prognosis prediction model incorporating multi-RNAs with pathologic distant metastasis (M) and pathologic primary tumor (T) (5-year AUC = 0.969, C-index = 0.812) had better efficiency than clinical prognosis prediction model (5-year AUC = 0.712, C-index = 0.680). In the constructed ceRNA regulatory network, lncRNA NCBP2-AS1 could interact with hsa-miR-34c and hsa-miR-363, and lncRNA LINC00115 could interact with hsa-miR-363 and hsa-miR-4709. SIX4, GRAP, NKAIN4, MMAA, and ERVMER34-1 are regulated by hsa-miR-4709. CONCLUSION Prognosis prediction model incorporating multi-RNAs with pathologic M and pathologic T may have great value in COAD prognosis prediction.
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Affiliation(s)
- Li Peng Jin
- Department of Colorectal & Anal Surgery, First Hospital Bethune of Jilin University, No. 71, Xinmin Street, Chaoyang District, Changchun, 130000 Jilin China
| | - Tao Liu
- Department of Colorectal & Anal Surgery, First Hospital Bethune of Jilin University, No. 71, Xinmin Street, Chaoyang District, Changchun, 130000 Jilin China
| | - Fan Qi Meng
- Department of Colorectal & Anal Surgery, First Hospital Bethune of Jilin University, No. 71, Xinmin Street, Chaoyang District, Changchun, 130000 Jilin China
| | - Jian Dong Tai
- Department of Colorectal & Anal Surgery, First Hospital Bethune of Jilin University, No. 71, Xinmin Street, Chaoyang District, Changchun, 130000 Jilin China
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Poursheikhani A, Abbaszadegan MR, Kerachian MA. Mechanisms of long non-coding RNA function in colorectal cancer tumorigenesis. Asia Pac J Clin Oncol 2020; 17:7-23. [PMID: 32970938 DOI: 10.1111/ajco.13452] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 08/03/2020] [Indexed: 12/14/2022]
Abstract
Colorectal cancer (CRC) is one of the most common cancers globally. Although a variety of CRC screening methods have been developed, many patients are diagnosed at advanced stages of CRC with tumor invasion and distance metastasis. Several studies have suggested the long noncoding RNAs (lncRNAs) as one of the main contributors in CRC tumorigenesis, although the exact underlying mechanism of lncRNAs in CRC is still unknown. Numerous studies have indicated aberrant expression of lncRNAs in CRC through different modes of action such as cell proliferation, apoptosis, cell cycle, DNA repair response, drug-resistance, migration, and metastasis. Furthermore, lncRNA polymorphisms can influence the risk of CRC development. Accordingly, lncRNAs can be served as promising diagnostic or prognostic biomarkers and also desired therapeutic targets affecting the outcome of patients with CRC. In this review, we summarized the updated and novel evidence that identifies different roles of lncRNAs in the tumorigenesis of CRC.
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Affiliation(s)
- Arash Poursheikhani
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Abbaszadegan
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Amin Kerachian
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Cancer Genetics Research Unit, Reza Radiotherapy, and Oncology Center, Mashhad, Iran
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Chen H, Luo J, Guo J. Identification of an alternative splicing signature as an independent factor in colon cancer. BMC Cancer 2020; 20:904. [PMID: 32962686 PMCID: PMC7510085 DOI: 10.1186/s12885-020-07419-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 09/15/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Colon cancer is a common malignant tumor with a poor prognosis. Abnormal alternative splicing (AS) events played a part in the occurrence and metastasis of the tumor. We aimed to develop a survival-associated AS signature in colon cancer. METHODS The Percent Spliced In values of AS events were available in The Cancer Genome Atlas (TCGA) SpliceSeq database. Univariate Cox analysis was carried out to detect the prognosis-related AS events. We created a predictive model on account of the survival-associated AS events, which was further validated with a training-testing group design. Kaplan-Meier analysis was applied to assess patient survival. The area under curve (AUC) of receiver operating characteristic (ROC) was performed to evaluate the predictive values of this model. Meanwhile, the clinical relevance of the signature and its regulatory relationship with splicing factors (SFs) were also evaluated. RESULTS In total, 2132 survival-related AS events were identified from colon cancer samples. We developed an eleven-AS signature, in which the 5-year AUC value was 0.911. Meanwhile, the AUC values at five years were 0.782 and 0.855 in the testing and entire cohort, respectively. Multivariate Cox regression displayed that the T category and the risk score of the signature were independent risk factors of colon cancer survival. Also, we constructed an SFs-AS network based on 11 SFs and 48 AS events. CONCLUSIONS We identified an eleven-AS signature of colon cancer. This signature could be treated as an independent prognostic factor.
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Affiliation(s)
- Haitao Chen
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071 China
| | - Jun Luo
- Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, 430071 China
- Wuhan University Center for Pathology and Molecular Diagnostics, Wuhan, 430071 China
| | - Jianchun Guo
- Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, 430071 China
- Wuhan University Center for Pathology and Molecular Diagnostics, Wuhan, 430071 China
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