MiR‑379‑5p inhibits cell proliferation and promotes cell apoptosis in non‑small cell lung cancer by targeting β‑arrestin‑1.

Abstract

Lung cancer is the most common fatal type of cancer, demonstrating high incidence rates in both sexes. Therefore, it is of vital importance to devise more effective and targeted therapies to improve the treatment quality for patients. The present study aimed to determine the effects of microRNA (miR)-379-5p on cell proliferation and apoptosis, in addition to its underlying molecular mechanisms in lung cancer. Tumor and adjacent normal tissues were obtained from patients with NSCLC and transfection experiments in A549 cells were performed using miR-379-5p mimics and pcDNA3.1- β-arrestin-1 (ARRB1) overexpression plasmids. The cell proliferation rate was determined using a Cell Counting Kit-8 assay and the cell apoptotic rate was analyzed using flow cytometry. Additionally, the mRNA and protein expression levels of proliferation-related signaling (PI3K, p-PI3K, AKT and p-AKT) and apoptotic-related factors (Bcl-2, Bax and caspase-3) were detected using reverse transcription-quantitative PCR and western blotting, respectively. The results of the present study revealed that miR-379-5p expression levels were downregulated, whereas ARRB1 expression levels were significantly upregulated in NSCLC tissues and cell lines. Following the successful transfection of the miR-379-5p mimic and ARRB1 overexpression plasmid, it was revealed that the overexpression of miR-379-5p inhibited cell proliferation and promoted cell apoptosis, whereas ARRB1 overexpression reversed this inhibition over proliferation and promotion of apoptosis. The increased cell apoptotic rate observed in the miR-379-5p mimics group was associated with a significant downregulation and upregulation of Bcl-2, and Bax and caspase-3 expression levels, respectively. Finally, ARRB1 was identified as a target gene of miR-379-5p. In conclusion, the expression levels of miR-379-5p were demonstrated to be significantly downregulated in lung cancer. In addition, miR-379-5p overexpression led to the decreased expression levels of Bcl-2, phosphorylated (p)-PI3K/PI3K and p-AKT/AKT, and the increased expression levels of Bax and caspase-3. Overall, this resulted in the inhibition of cell proliferation and promoted cell apoptosis by directly targeting ARRB1. Therefore, miR-379-5p may be a potential target for NSCLC treatment due to its ability to inhibit cell proliferation and accelerate the apoptotic process.