miR-142-3p improves paclitaxel sensitivity in resistant breast cancer by inhibiting autophagy through the GNB2-AKT-mTOR Pathway

Breast cancer has overtaken lung cancer as the most prevalent cancer worldwide. The development of advanced drug resistance inhibits the efficacy of paclitaxel(PTX)as a first-line chemotherapeutic agent for breast cancer. Autophagy and microRNAs (miRNAs) play a key role in chemoresistance. This study investigated the miR-142-3p effect on PTX resistance by regulating autophagy. A PTX-resistant breast cancer cell line was constructed, and miR-142-3p and G protein beta polypeptide 2 (GNB2) were filtered out using RNA sequencing and protein microarray analysis. The study revealed that miR-142-3p expression was lower in drug-resistant cells compared parental cells. Higher miR-142-3p expression inhibited the viability, migration, and autophagic flux of drug-resistant cells, while promoting apoptosis and sensitivity to PTX treatment. Mechanistically, miR-142-3p was found to amend PTX resistance by targeting GNB2, further revealing that the knockdown of GNB2 expression could activate the AKT-mTOR pathway. This study suggests that GNB2 is an essential target for miR-142-3p to restrain autophagy, providing a new reference value for improving breast cancer PTX treatment.