miR‑29a‑3p inhibits the malignant characteristics of non‑small cell lung cancer cells by reducing the activity of the Wnt/β‑catenin signaling pathway

Abstract

MicroRNAs (miRNAs) can influence non-small cell lung cancer (NSCLC) in a tumor-suppressive and oncogenic manner. The present study aimed to investigate the effects and underlying mechanisms of miR-29a-3p in NSCLC. NSCLC cell lines (A549, H1299, and H460) and a normal lung epithelial cell line (BEAS-2B) were used. Additionally, a mouse lung tumor xenograft model was established using A549 cells and used to determine the effects of miR-29a-3p on NSCLC in vivo. Tumor volumes were measured every week. The expression of miR-29a-3p in cells and lung tissues were detected by RT-qPCR. Cell proliferation was detected using Cell Counting Kit-8 and EdU assays. Migration and invasion were assessed using wound healing and Transwell invasion assays, respectively. Ki-67 expression was detected using immunohistochemical staining. The expression levels of Wnt3a and β-catenin were determined using western blotting. miR-29a-3p expression was significantly downregulated in NSCLC cells and mice. In contrast to miR-29a-3p knockdown, miR-29a-3p overexpression decreased NSCLC cell proliferation, migration, and invasion as well as tumor growth in in the NSCLC mouse model. Moreover, miR-29a-3p overexpression decreased the protein expression levels of Wnt3a and β-catenin. The inhibitory effects of miR-29a-3p on NSCLC cells were reversed by LiCl (an activator of the Wnt signaling pathway). In conclusion, miR-29a-3p prevented NSCLC tumor growth and cell proliferation, migration, and invasion by inhibiting the Wnt/β-catenin signaling pathway. This finding offers novel insights into the prognosis and treatment of NSCLC.

MiR-1246b, a novel miRNA molecule of extracellular vesicles in bronchoalveolar lavage fluid, promotes nodule growth through FGF14 in patients with lung cancer

“…MiRNA alterations in EVs have been extensively studied in the diagnosis, treatment and pathogenesis of lung cancers. In addition to the effect on the malignant development of lung cancers, it has also been found that miR-223-3p and miR-29a-3p can inhibit the proliferation and migration of non-small cell lung cancer (NSCLC) cells [ 27 , 28 ]. The source of these research samples is mainly the peripheral blood of patients.…”

Correlation between Circulating miR-16, miR-29a, miR-144 and miR-150, and the Radiotherapy Response and Survival of Non-Small-Cell Lung Cancer Patients

“…Regarding miR-29a, its downregulation in NSCLC patients has been observed in multiple studies, highlighting its potential tumor-suppressive role [ 46 , 47 ]. Additionally, miR-29a has been shown to reduce the activity of the Wnt/β-catenin signaling pathway in NSCLC cells, which is associated with tumor growth and progression [ 48 ]. MiR-144 has been reported to be downregulated in various tumor entities and has functions as a tumor suppressor by inhibiting cell proliferation, invasion, metastasis and tumor growth [ 29 , 49 , 50 ].…”