Research Article: MicroRNA-582-5p suppresses non-small cell lung cancer cells growth and invasion via downregulating NOTCH1

Date Published: June 6, 2019

Publisher: Public Library of Science

Author(s): Jianghong Liu, Shengshuo Liu, Xiaoyan Deng, Jiaoyu Rao, Kaiyuan Huang, Gengrui Xu, Xiaokang Wang, Klaus Roemer.

http://doi.org/10.1371/journal.pone.0217652

Abstract

Non-small cell lung cancer (NSCLC) is the most common cancer worldwide. MicroRNAs have been shown to be correlated with biological processes of various tumors. In this study, we observed that the expression of miR-582-5p was lower in NSCLC tissues than that in para-carcinoma tissues. Ectopic expression of miR-582-5p significantly inhibited NCI-H358 cell proliferation and invasion. Knockdown of miR-582-5p showed the opposite results, with cell growth rate and the invasive capacity of PC-9 cells enhanced. Furthermore, we elucidated that NOTCH1 is a target of miR-582-5p and there is an inverse correlation between miR-582-5p and NOTCH1 expression in NSCLC tissues. Overexpression of NOTCH1 in miR-582-5p-overexpressing NCI-H358 cells could partially reverse the inhibition of cell proliferation and invasion by miR-582-5p. Thus, our research demonstrated that miR-582-5p suppresses NSCLC cell lines’ growth and invasion via targeting oncoprotein NOTCH1 and restoration of miR-582-5p might be feasible therapeutic strategy for NSCLC.

Partial Text

Lung cancer is the main cause of cancer-associated mortality all around the world and every year, about 1.6 million people die of lung cancer[1]. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are two subtypes of lung cancer. NSCLC, including adenocarcinoma, squamous cell carcinoma and large cell carcinoma, makes up approximately 85% of all lung cancer cases. Although technologies and strategies for treating NSCLC have improved in recent years, the prognosis of this disease is still poor. The 5-year survival rate of NSCLC is just around 15%[2]. It has been reported that tissue levels of specific microRNAs is associated with the pathological development of different cancers and overwhelming evidences have indicated that microRNAs can serve as potential diagnostic and prognostic biomarkers for various types of cancer[3, 4]. Therefore, searching new biomarkers and elucidating the underlying mechanism are fundamental for the development of new therapeutic treatments in NSCLC.

Increasing evidence demonstrate that miRNAs take part in tumorigenesis and progression via targeting tumor suppressive genes or oncogenes, which are associated with cancer cell growth, migration, invasion, angiogenesis and apoptosis[21]. Previous studies demonstrated that miR-582-5p exhibits different effects against different kinds of cancers. In human endometrial carcinoma, up-regulating the expression of miR-582-5p could inhibit cell proliferation and induce apoptosis. Further mechanism study showed that miR-582-5p exerted the inhibitory effect through targeting AKT3[22]. Study by Wang et al described that miR-582-5p suppressed metastasis of salivary adenoid cystic carcinoma cells via targeting FOXC1[9]. In gastric cancer, miR-582-5p has been verified to restrain cell growth by down-regulating the expression of AKT3[23]. Uchino et al clarified that miR-582-5p and miR-582-3p functioned effectively in the inhibition of bladder cancer progression[24]. However, D.H. et al proved that miR-582-5p characterized anti-apoptotic function, promoting human glioblastoma stem cell survival via directly inhibiting caspase 3, caspase 9, and Bim[25]. Study by Maeno et al demonstrated that up-regulation of miR-582-5p facilitated cellular proliferation of prostate cancer cells under androgen-deprived conditions[11].In colorectal cancer, miR-582-5p has showed to elevate cell growth rate by targeting adenomatous polyposis coli (APC)[26]. The exact function of miR-582-5p in NSCLC remains unknown.

 

Source:

http://doi.org/10.1371/journal.pone.0217652