MiR‐376a suppresses the proliferation and invasion of non‐small‐cell lung cancer by targeting c‐Myc

Abstract

It has been reported that miR-376a is involved in the formation and progression of several types of cancer. However, the expression and function of miR-376a is still unknown in non-small cell lung carcinomas (NSCLC). In this study, the expression of miR-376a in NSCLC tissues and cell lines were examined by real-time PCR, the effects of miR-376a on cell proliferation, apoptosis and invasion were evaluated in vitro. Luciferase reporter assay was performed to identify the targets of miR-376a. The results showed that miR-376a was significantly downregulated in NSCLC tissues and cell lines. Restoration of miR-376a in NSCLC cell line A549 significantly inhibited cell proliferation, increased cell apoptosis and suppressed cell invasion, compared with control-transfected A549 cells. Luciferase reporter assay showed that c-Myc, an oncogene that regulating cell survival, angiogenesis and metastasis, was a direct target of miR-376a. Over-expression of miR-376a decreased the mRNA and protein levels of c-Myc in A549 cells. In addition, upregulation of c-Myc inhibited miR-376a-induced inhibition of cell proliferation and invasion in A549 cells. Therefore, our results indicate a tumor suppressor role of miR-376a in NSCLC by targeting c-Myc. miR-376a may be a promising therapeutic target for NSCLC.

MicroRNA‑376a inhibits cell proliferation and invasion in osteosarcoma via directly targeting SATB1

“…Formosa et al (18) demonstrated that the resumption of miR-376a expression attenuates the growth of prostate cancer cells while inducing apoptosis. Wang et al (19) indicated that miR-376a re-expression restricts cell proliferation and invasion while promoting apoptosis in non-small-cell lung cancer. Conversely, miR-376a serves oncogenic roles in ovarian cancer by promoting cell proliferation and motility, inhibiting cell apoptosis in vitro and increasing tumor growth in vivo (29).…”

“…Therefore, the expression and roles of miRs in OS must be further investigated to identify potential therapeutic targets for the therapy of patients with OS. miR-376a-3p (miR-376a) is dysregulated in several human cancer types and the dysregulation of miR-376a serves an important role in various cell processes, including cell proliferation, migration, invasion, metastasis and apoptosis (16)(17)(18)(19). However, to the best of our knowledge, the expression pattern, clinical significance, specific role and detailed mechanisms of miR-376a in OS remains unclear.…”

Effect of gga-miR-155 on cell proliferation, apoptosis and invasion of Marek’s disease virus (MDV) transformed cell line MSB1 by targeting RORA

“…The 5′terminal seed sequences of mature miRNAs regulate target gene expression at the post-transcriptional level by binding to the 3′-UTR of the target mRNAs, which results in their degradation or translational suppression [29,33]. The biological role of miRNAs has gained considerable attention in recent years, and several have been identified as oncogenes or tumor suppressor genes that regulate proliferation, differentiation, apoptosis and migration of cancer cells [34,35]. Therefore, miRNAs are potential markers for the diagnosis, prognosis, classification, staging and therapeutic monitoring of cancers.…”

A review of microRNAs related to the occurrence, diagnosis, and prognosis of non-small cell lung cancer

“…Apart from their roles as tumor promoters, some miRNAs function as tumor suppressors by targeting oncogenes. In NSCLC tissues and cell lines, miR-376a was significantly downregulated; the overexpression of miR-376a could inhibit cell proliferation and inva-sion and alsp increase cell apoptosis by decreasing the mRNA and protein levels of c-Myc [23] . MiRNA-183 has been considered a tumor suppressor, which can inhibit the proliferation, migration and invasion of NSCLC cells by targeting MTA1 [24] .…”