miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting CDKN1C, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs

Autor:	Xiongwen Zhang, Fangqing Zhao, Lixing Feng, Xiaofan Gu, Mingshi Xu, Zhongmin Yang
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	0301 basic medicine Cancer Research CDKN1C T cell colorectal cancer Drug resistance Cyclin-dependent kinase inhibitor 1C Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine microRNA Medicine miR-92b-3p RC254-282 business.industry apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens chemoresistance Cell cycle Multiple drug resistance 030104 developmental biology medicine.anatomical_structure Oncology Paclitaxel chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research cell cycle business
Zdroj:	Cancers Volume 13 Issue 13 Cancers, Vol 13, Iss 3323, p 3323 (2021)
ISSN:	2072-6694
DOI:	10.3390/cancers13133323
Popis:	Simple Summary Multidrug resistance (MDR) limits the effectiveness of colorectal cancer (CRC) treatment and miRNAs play an important role in drug resistance. To search for miRNA targets that may be involved in the CRC MDR phenotype, this study used small RNAomic screens to analyze the expression profiles of miRNAs in CRC HCT8 cell line and its chemoresistant counterpart HCT8/T cell line. It was found that miR-92b-3p was highly expressed in HCT8/T cells and chemotherapeutic drugs could stimulate CRC cells to up-regulate miR-92b-3p expression and conferred cellular resistance to chemotherapeutic drugs. This study revealed a new mechanism of MDR in CRC, elucidating for the first time the direct link between miR-92b-3p/CDKN1C and chemoresistance. In summary, this study suggested that miR-92b-3p could be used as a potential therapeutic target for reversing MDR in chemotherapy and as a candidate biomarker for predicting the efficacy of chemotherapy. Abstract Colorectal cancer (CRC) is the third most common malignant tumor in the world and the second leading cause of cancer death. Multidrug resistance (MDR) has become a major obstacle in the clinical treatment of CRC. The clear molecular mechanism of MDR is complex, and miRNAs play an important role in drug resistance. This study used small RNAomic screens to analyze the expression profiles of miRNAs in CRC HCT8 cell line and its chemoresistant counterpart HCT8/T cell line. It was found that miR-92b-3p was highly expressed in HCT8/T cells. Knockdown of miR-92b-3p reversed the resistance of MDR HCT8/T cells to chemotherapeutic drugs in vitro and in vivo. Paclitaxel (PTX, a chemotherapy medication) could stimulate CRC cells to up-regulate miR-92b-3p expression and conferred cellular resistance to chemotherapeutic drugs. In studies on downstream molecules, results suggested that miR-92b-3p directly targeted Cyclin Dependent Kinase Inhibitor 1C (CDKN1C, which encodes a cell cycle inhibitor p57Kip2) to inhibit its expression and regulate the sensitivity of CRC cells to chemotherapeutic drugs. Mechanism study revealed that the miR-92b-3p/CDKN1C axis exerted a regulatory effect on the sensitivity of CRC cells via the regulation of cell cycle and apoptosis. In conclusion, these findings showed that miR-92b-3p/CDKN1C was an important regulator in the development of drug resistance in CRC cells, suggesting its potential application in drug resistance prediction and treatment.
Databáze:	OpenAIRE
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