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      MicroRNA-Related Prognosis Biomarkers from High-Throughput Sequencing Data of Colorectal Cancer

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          Abstract

          Background

          Colorectal cancer (CRC) is the third most common cancer in the world, and most of them are adenocarcinomas. CRC could be classified as colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) according to the original tumorigenesis position. Increasing evidences indicated that microRNAs (miRNAs) play an important role in the occurrence of multiple tumors.

          Methods

          In this study, we firstly downloaded miRNA (COAD, 8 controls vs. 455 tumors; READ, 3 controls vs. 161 tumors) and mRNA (COAD, 41 controls vs. 478 tumors; READ, 10 controls vs. 166 tumors) data from The Cancer Genome Atlas (TCGA) database and then used DESeq2, RegParallel, miRDB, TargetScanHuman 7.2, DAVID 6.8, STRING, and Cytoscape software to identify the potential prognosis biomarkers.

          Results

          We identified 175 differential expression miRNAs (DEMs) and 3747 differential expression genes (DEGs) in COAD and 184 DEMs and 3928 DEGs in READ. And then, we obtained 21 (13 in COAD and 8 in READ) DEMs associated with the survival rates, which correlated with 440 (217 in COAD and 223 in READ) overlapping DEGs. Through survival analysis for those overlapping DEGs, we found 11 (8 in COAD and 3 in READ) overlapping DGEs associated with survival rates of patients, which were correlated with 9 (7 in COAD and 2 in READ) DEMs significantly.

          Conclusion

          In this study, we found several candidate prognostic biomarkers which have been identified in various cancers and also found several new prognosis biomarkers of COAD and READ. In conclusion, this analysis based on theoretical knowledge and clinical outcomes we have done needs further confirmation by more researches.

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          Most cited references35

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          miRDB: an online database for prediction of functional microRNA targets

          Abstract MicroRNAs (miRNAs) are small noncoding RNAs that act as master regulators in many biological processes. miRNAs function mainly by downregulating the expression of their gene targets. Thus, accurate prediction of miRNA targets is critical for characterization of miRNA functions. To this end, we have developed an online database, miRDB, for miRNA target prediction and functional annotations. Recently, we have performed major updates for miRDB. Specifically, by employing an improved algorithm for miRNA target prediction, we now present updated transcriptome-wide target prediction data in miRDB, including 3.5 million predicted targets regulated by 7000 miRNAs in five species. Further, we have implemented the new prediction algorithm into a web server, allowing custom target prediction with user-provided sequences. Another new database feature is the prediction of cell-specific miRNA targets. miRDB now hosts the expression profiles of over 1000 cell lines and presents target prediction data that are tailored for specific cell models. At last, a new web query interface has been added to miRDB for prediction of miRNA functions by integrative analysis of target prediction and Gene Ontology data. All data in miRDB are freely accessible at http://mirdb.org.
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            Survival after laparoscopic surgery versus open surgery for colon cancer: long-term outcome of a randomised clinical trial.

            Laparoscopic surgery for colon cancer has been proven safe, but debate continues over whether the available long-term survival data justify implementation of laparoscopic techniques in surgery for colon cancer. The aim of the COlon cancer Laparoscopic or Open Resection (COLOR) trial was to compare 3-year disease-free survival and overall survival after laparoscopic and open resection of solitary colon cancer. Between March 7, 1997, and March 6, 2003, patients recruited from 29 European hospitals with a solitary cancer of the right or left colon and a body-mass index up to 30 kg/m(2) were randomly assigned to either laparoscopic or open surgery as curative treatment in this non-inferiority randomised trial. Disease-free survival at 3 years after surgery was the primary outcome, with a prespecified non-inferiority boundary at 7% difference between groups. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, and blood loss during surgery. Neither patients nor health-care providers were blinded to patient groupings. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00387842. During the recruitment period, 1248 patients were randomly assigned to either open surgery (n=621) or laparoscopic surgery (n=627). 172 were excluded after randomisation, mainly because of the presence of distant metastases or benign disease, leaving 1076 patients eligible for analysis (542 assigned open surgery and 534 assigned laparoscopic surgery). Median follow-up was 53 months (range 0.03-60). Positive resection margins, number of lymph nodes removed, and morbidity and mortality were similar in both groups. The combined 3-year disease-free survival for all stages was 74.2% (95% CI 70.4-78.0) in the laparoscopic group and 76.2% (72.6-79.8) in the open-surgery group (p=0.70 by log-rank test); the difference in disease-free survival after 3 years was 2.0% (95% CI -3.2 to 7.2). The hazard ratio (HR) for disease-free survival (open vs laparoscopic surgery) was 0.92 (95% CI 0.74-1.15). The combined 3-year overall survival for all stages was 81.8% (78.4-85.1) in the laparoscopic group and 84.2% (81.1-87.3) in the open-surgery group (p=0.45 by log-rank test); the difference in overall survival after 3 years was 2.4% (95% CI -2.1 to 7.0; HR 0.95 [0.74-1.22]). Our trial could not rule out a difference in disease-free survival at 3 years in favour of open colectomy because the upper limit of the 95% CI for the difference just exceeded the predetermined non-inferiority boundary of 7%. However, the difference in disease-free survival between groups was small and, we believe, clinically acceptable, justifying the implementation of laparoscopic surgery into daily practice. Further studies should address whether laparoscopic surgery is superior to open surgery in this setting.
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              Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer.

              We have previously shown that miR-486-5p is one of the most downregulated micro RNAs in lung cancer. The objective of the study was to investigate the role of miR-486-5p in the progression and metastasis of non-small-cell lung cancer (NSCLC). We evaluated miR-486-5p expression status on 76 frozen and 33 formalin-fixed paraffin-embedded tissues of NSCLC by quantitative reverse transcriptase PCR to determine its clinicopathologic significance. We then performed function analysis of miR-486-5p to determine its potential roles on cancer cell migration and invasion in vitro and metastasis in vivo. We also investigated the target genes of miR-486-5p in lung tumorigenesis. miR-486-5p expression level was significantly lower in lung tumors compared with their corresponding normal tissues (P<0.0001), and associated with stage (P=0.0001) and lymph node metastasis of NSCLC (P=0.0019). Forced expression of miR-486-5p inhibited NSCLC cell migration and invasion in vitro and metastasis in mice by inhibiting cell proliferation. Furthermore, ectopic expression of miR-486-5p in cancer cells reduced ARHGAP5 expression level, whereas miR-486-5p silencing increased its expression. Luciferase assay demonstrated that miR-486-5p could directly bind to the 3'-untranslated region of ARHGAP5. The expression level of miR-486-5p was inversely correlated with that of ARHGAP5 in lung tumor tissues (P=0.0156). Reduced expression of ARHGAP5 considerably inhibited lung cancer cell migration and invasion, resembling that of miR-486-5p overexpression. miR-486-5p may act as a tumor-suppressor contributing to the progression and metastasis of NSCLC by targeting ARHGAP5. miR-486-5p would provide potential diagnostic and therapeutic targets for the disease.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2020
                9 September 2020
                : 2020
                Affiliations
                1Xiangya Hospital, Central South University, Changsha, 410078 Hunan, China
                2Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, School of Public Health and Laboratory Medicine, Hunan University of Medicine, Huaihua, 418000 Hunan, China
                3Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, 100193 Beijing, China
                Author notes

                Guest Editor: Hongliang Liu

                Article
                10.1155/2020/7905380
                7501550
                8d8b2d65-2eb2-416c-8ebd-a79bc7d4a028
                Copyright © 2020 Xiao-Liang Xing et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funding
                Funded by: Huaihua Science and Technology Department
                Award ID: 2020R3104
                Funded by: China Postdoctoral Science Foundation
                Award ID: 2020TQ0365
                Funded by: Hunan University of Medicine
                Award ID: JYKY1901
                Funded by: Education Department of Hunan Province
                Award ID: 19C1327
                Award ID: 19A354
                Funded by: Natural Science Foundation of Hunan Province
                Award ID: 2019JJ40204
                Categories
                Research Article

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