https://scholars.lib.ntu.edu.tw/handle/123456789/572927
標題: | In vitro and in silico mechanistic insights into miR-21-5p-mediated topoisomerase drug resistance in human colorectal cancer cells | 作者: | JEN-CHIH CHEN Hsieh Y.-Y Lo H.-L Li A Chou C.-J Yang P.-M. |
關鍵字: | caspase 3; complementary DNA; DNA topoisomerase inhibitor; doxorubicin; etoposide; firtecan; fluorouracil; messenger RNA; microRNA 21; microRNA 21 5p; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; proteasome; unclassified drug; DNA topoisomerase; DNA topoisomerase inhibitor; microRNA; MIRN21 microRNA, human; apoptosis; Article; autophagy; bioinformatics; cancer patient; cancer prognosis; cancer resistance; cancer survival; cell proliferation; cell viability; cell viability assay; cohort analysis; colorectal cancer cell line; computer model; DLD-1 cell line; down regulation; enzyme activity; gene overexpression; human; human cell; in vitro study; major clinical study; metastasis free survival; nuclear reprogramming; overall survival; stable expression; upregulation; autophagy; colorectal tumor; computer simulation; drug effect; drug resistance; gene expression regulation; genetics; metabolism; pathology; tumor cell line; Autophagy; Cell Line, Tumor; Colorectal Neoplasms; Computer Simulation; DNA Topoisomerases; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Topoisomerase Inhibitors | 公開日期: | 2019 | 卷: | 9 | 期: | 9 | 來源出版物: | Biomolecules | 摘要: | Although chemotherapy for treating colorectal cancer has had some success, drug resistance and metastasis remain the major causes of death for colorectal cancer patients. MicroRNA-21-5p (hereafter denoted as miR-21) is one of the most abundant miRNAs in human colorectal cancer. A Kaplan-Meier survival analysis found a negative prognostic correlation of miR- 21 and metastasis-free survival in colorectal cancer patients (The Cancer Genome Atlas Colon Adenocarcinoma/TCGA-COAD cohort). To explore the role of miR-21 overexpression in drug resistance, a stable miR-21-overexpressing clone in a human DLD-1 colorectal cancer cell line was established. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay found that miR-21 overexpression induced drug resistance to topoisomerase inhibitors (SN- 38, doxorubicin, and etoposide/VP-16). Mechanistically, we showed that miR-21 overexpression reduced VP-16-induced apoptosis and concomitantly enhanced pro-survival autophagic flux without the alteration of topoisomerase expression and activity. Bioinformatics analyses suggested that miR-21 overexpression induced genetic reprogramming that mimicked the gene signature of topoisomerase inhibitors and downregulated genes related to the proteasome pathway. Taken together, our results provide a novel insight into the role of miR-21 in the development of drug resistance in colorectal cancer. ? 2019 by the authors. Licensee MDPI, Basel, Switzerland. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85072047482&doi=10.3390%2fbiom9090467&partnerID=40&md5=c93ec90775cd50824865b83b403521c5 https://scholars.lib.ntu.edu.tw/handle/123456789/572927 |
ISSN: | 2218273X | DOI: | 10.3390/biom9090467 |
顯示於: | 生物科技研究所 |
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