MiR-29c reduces the cisplatin resistance of non-small cell lung cancer cells by negatively regulating the PI3K/Akt pathway

Abstract

In previous studies, miR-29s showed tumor suppressor properties against lung cancer, which improved the survival of patients upon the administration of chemotherapy via an unknown mechanism. Here, we investigated the regulatory effects of miR-29s on the cisplatin resistance of NSCLC cells. The expression of miR-29s was assessed in 130 clinical patients and in cisplatin-treated NSCLS cell lines. MiR-29c expression was decreased in 77% of NSCLC patients. Cisplatin treatment increased the expression of miR-29c and decreased the expression of its oncogenic target AKT2 in NSCLC cell lines. A Kaplan–Meier survival analysis indicated that higher miR-29c levels led to a longer disease-free survival. In particular, patients who experienced cancer recurrences after cisplatin chemotherapy exhibited a lower level of miR-29c expression, suggesting that miR-29c activation may contribute to the chemotherapeutic efficiency of cisplatin. The enforced expression of miR-29c enhanced the cisplatin sensitivity of NSCLC cells, while the knocking down of miR-29c led to cisplatin resistance. MiR-29c amplified the therapeutic effects of cisplatin in vivo. Rescue experiments suggested that miR-29c regulates the cisplatin resistance of NSCLS cells by negatively regulating the PI3K/Akt pathway. Overall, our results demonstrated that miR-29c enhances the sensitivity of NSCLC cells to cisplatin by targeting the PI3K/Akt pathway.

Exosomal microRNAs from Longitudinal Liquid Biopsies for the Prediction of Response to Induction Chemotherapy in High-Risk Neuroblastoma Patients: A Proof of Concept SIOPEN Study ‖

“…Hypoxia is a condition of low oxygen tension occurring in solid tumor microenvironment, associated with malignant tumor aggressiveness, and we have previously shown it to be an independent prognostic factor in NB, negatively correlating with tumor outcome [64]. MiR-29c is also a tumor-suppressor miRNA: its expression enhanced the sensitivity of non-small cell lung cancer cells to cisplatin by targeting the PI3K/Akt pathway [65]. Let-7b belongs to the let-7 family, a group of tumor suppressor miRNAs, implicated in numerous cancers, including NB.…”

Transthyretin (TTR) Suppressed Tumor Progression in Non-Small Cell Lung Cancer by Inactivating MAPK/ERK Pathway

“…The tumor associated pathways, such as Wnt, PI3K/AKT or NF-kB, may play an important role in the development of tumorigenesis [24][25][26][27][28][29][30]. Further, there is increasing evidence that typical MPAK/ERK signaling pathway is a pivotal signaling pathway involved in the development of several cancers [31][32][33][34][35][36].…”

Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine

“…[40–52]. It has been reported that high miR-29c expression increased the sensitivity of non-small cell lung cancer (NSCLC) cells to the cisplatin [53]. Wang et al found that miR-29c overexpression might contribute to the efficacy of cisplatin in gastric cancer treatment [54].…”