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Recent Patents on Anti-Cancer Drug Discovery

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ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

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Research Article

Downregulation of miRNA-14669 Reverses Vincristine Resistance in Colorectal Cancer Cells through PI3K/AKT Signaling Pathway

Author(s): Weihua Dong, Fang Wang, Qingyu Liu, Tianyun Wang*, Yun Yang, Peixia Guo, Xiang Li and Bingdi Wei

Volume 17, Issue 2, 2022

Published on: 06 August, 2021

Page: [178 - 186] Pages: 9

DOI: 10.2174/1574892816666210806154225

Price: $65

Abstract

Background: Vincristine (VCR) is a chemotherapeutic drug commonly used in the treatment of Colorectal Cancer (CRC). However, VCR drug resistance may result in reduced efficacy and even failure of chemotherapy in CRC treatment. MiRNA has been demonstrated to be associated with the sensitivity of tumor cells to chemotherapy.

Objectives: This study aimed to identify a novel miRNA-14669 that can reverse vincristine resistance and sensitize drug-resistant colorectal cancer cells.

Methods: High-throughput sequencing was performed to screen miRNAs that are associated with VCR drug resistance, and qRT-PCR was used for further validation. The miRNA mimic and inhibitor were designed and transfected into HCT-8,HCT-116 and HCT-8/VCR cells. Wound healing test examined the effect of the miRNA on the migration of colorectal cancer cells. Flow cytometry was used to evaluate cell apoptosis of HCT-8 cells. Survivin, Bcl-2, GST3, MDR1 and MRP1 expressions were detected by Western blot.

Results: The expression of miRNA-14669 in HCT-8/VCR cells was 1.925 times higher than that of the HCT-8 cells. After transfecting with mimic miRNA, HCT-8 and HCT-116 cells showed an increased survival rate. The survival rate of HCT-8/VCR cells decreased by transfection of inhibitor. The inhibitor also sensitized HCT-8 and HCT-116 cells to VCR or 5-Fluorouracil (5-FU). The migratory ability of HCT-8 and HCT-116 cells increased by miRNA mimic while reduced by miRNA inhibitor. Overexpression of miRNA-14669 reduced apoptosis, while downregulation of miRNA- 14669 increased cell apoptosis in HCT-8 cells. The mechanism of the miRNA involved in drug resistance may be attributed to apoptosis of tumor cells, detoxification of GST3 and drug efflux induced by MDR1 and MRP1. PI3K / AKT is the signaling pathway related to drug resistance.

Conclusion: We identified a novel miRNA-14669 that may be associated with the chemotherapeutic resistance in CRC cells.

Keywords: miRNA, identify, drug resistance, colorectal cancer, reverse, regulation.

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