Hsa-miR-329 exerts tumor suppressor function through down-regulation of MET in non-small cell lung cancer

Abstract

MicroRNAs (miRNAs) act as key regulators of multiple cancers. Hsa-miR-329 (miR-329) functions as a tumor suppressor in some malignancies. However, its role on lung cancer remains poorly understood. In this study, we investigated the role of miR-329 on the development of lung cancer. The results indicated that miR-329 was decreased in primary lung cancer tissues compared with matched adjacent normal lung tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-329 in lung cancer cell lines substantially repressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibiting cyclin D1, cyclin D2 and up-regulatiing p57(Kip2) and p21(WAF1/CIP1). In addition, miR-329 promoted NSCLC cell apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-329 inhibited cellular migration and invasiveness through inhibiting matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene MET was revealed to be a putative target of miR-329, which was inversely correlated with miR-329 expression. Furthermore, down-regulation of MET by siRNA performed similar effects to over-expression of miR-329. Collectively, our results demonstrated that miR-329 played a pivotal role in lung cancer through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic MET.

Expression level of EGFR and MET receptors regulates invasiveness of melanoma cells

“…Our results indicate that expression of MET receptor is also crucial for the proteolytic activity of melanoma cells—decreased digestion of fluorescently labelled gelatin and MMP‐9 activity were observed in melanoma cells with diminished level of this protein. Similar effect was observed by Sun et al who showed that MiR‐329 caused down‐regulation of MET expression what led to decreased mRNA level of MMP‐7 and MMP‐9 and thus reduced cellular migration and invasiveness of lung cancer cells.…”

The Novel miR-9600 Suppresses Tumor Progression and Promotes Paclitaxel Sensitivity in Non–small-cell Lung Cancer Through Altering STAT3 Expression

“…5,19,38,39,40,41 miRNAs may act as tumor suppressor and are usually downregulated in cancer tissue. For example, the miR-206 is downregulated in NSCLC and suppresses the proliferation of A549 and SK-MES-1 cells.…”

“…11,12,13,14 miRNAs have been involved in various of biological processes corrected with tumor initiation, development and progression, including tumor cell growth and metastasis, cell identity, senescence, apoptosis, and stem cell maintenance. 15,16,17,18,19 Cui and his colleagues reported that miR-224 promoted tumor progression in non–small-cell lung cancer partially antagonist functions of SMAD4 and TNFAIP1. 20 And another miRNA, namely miR-31, predicted the presence of lymph node metastases and survival in patients with lung adenocarcinoma.…”

miR-134: A Human Cancer Suppressor?

“…Additionally, miRNAs are described as a kind of emerging clinical, diagnostic, and prognostic biomarker, as well as treatment approach 9, 10. Sun et al 11, 12, 13, 14, 15. have explored the association between miRNAs and non-small cell lung cancer (NSCLC), revealing miR-139-5p, miR-187, miR-206, miR-326, and miR-329 were downregulated in lung cancer cell lines and tissues and played tumor-suppressive roles by targeting specific 3′ UTR of mRNAs for several oncogenes.…”