Elucidation of the mechanism of paclitaxel resistance by microRNA functional analysis and overcoming refractoriness

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08971
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Osaka Medical and Pharmaceutical University
• Principal Investigator: Kimura Kosei 大阪医科薬科大学, 医学部, 講師 (20623846)
• Co-Investigator(Kenkyū-buntansha): 谷口 高平 大阪医科薬科大学, 医学部, 講師 (70779686)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: micro RNA / パクリタキセル耐性株 / ABCB1 / 抗癌剤耐性

Outline of Final Research Achievements

Progressive recurrent breast cancer has a poor prognosis, primarily due to the acquisition of drug resistance. This study aimed to elucidate the mechanism of drug resistance to Paclitaxel (PTX) through changes in the expression of microRNAs (miRNAs). Next-generation sequencing analysis of miRNAs was performed on MCF-7 (parental) and MCF-7/PTXR (resistant) cell lines to identify miRNAs associated with drug resistance, including those targeting the known drug resistance gene ABCB1. The results suggested that miRNA-455-3p is involved in the mechanism of drug resistance. Introducing miRNA-455-3p into the resistant cell line resulted in decreased expression of ABCB1 and partial reversal of PTX resistance.

Free Research Field

乳腺外科

Academic Significance and Societal Importance of the Research Achievements

本研究からmiRNA-455-3pの発現低下によりABCB1の発現が亢進し、PTX耐性に寄与した可能性が示唆された。miRNAの導入実験から、miRNA-455-3pがABCB1の翻訳抑制を介し、PTX耐性を一部解除していることも示唆された。PTXはABCB1の基質であり、ABCB1タンパクの発現低下によりPTXの排出が抑制される。この研究は、miRNA-455-3pがPTX耐性の調節に重要な役割を果たすことを明らかにし、ABCB1を標的とした新たな治療戦略の可能性や、PTX耐性の機序解明を通じて、耐性克服のための新規治療法やサロゲートマーカーの開発に向けた基盤を提供する点でも重要である。