Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1\u03b1

Qiguang Chen,Shu-Qi Du,Ze-Liang Li,Jun Li,Chui-Ze Kong,Wei Zhou,Xian-Kui Liu,Zhen-Hua Li,Da-Xin Gong,Jian-Bin Bi,Zhe Zhang

doi:10.1186/s12935-019-0782-5

Abstract

BackgroundCumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer. However, the expression status and involvement of SNHG12 in renal cell carcinoma is still elusive.MethodsThe expression of SNHG12 was determined by q-PCR. The transcriptional regulation was interrogated by luciferase reporter assay. Cell viability was measured with CCK-8 kit. The anchorage-independent was evaluated by soft agar assay. Cell apoptosis was analyzed by Annexin V/7-AAD double staining. The migration and invasion were determined by trans-well assay and wound scratch closure. The in vivo tumor growth was monitored in xenograft mice model. Protein expression was quantified by immunoblotting.ResultsSNHG12 was aberrantly up-regulated in renal carcinoma both in vivo and in vitro. High expression of SNHG12 associated with poor prognosis. Deficiency of SNHG12 significantly suppressed cell viability, anchorage-independent growth and induced apoptosis. In addition, SNHG12 silencing inhibited migrative and invasive in vitro and xenograft tumor growth in vivo. Mechanistically, SNHG12 modulated HIF1α expression via competing with miR-199a-5p, which consequently contributed to its oncogenic potential. MiR-199a-5p inhibition severely compromised SNHG12 silencing-elicited tumor repressive effects.ConclusionOur data uncovered a crucial role of SNHG12-miR-199a-5p-HIF1α axis in human renal cancer.

Highlights

Cumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer
SNHG12‐knockdown inhibited cell viability, anchorage‐independent colony formation and induced apoptosis in renal cancer cells Our previous results demonstrated that over-expression of SNHG12 was prevalent in renal carcinoma, which intimately associated with poor outcomes
The shRNA-mediated knockdown of SNHG12 was first confirmed by quantitative PCR at 24, 48 and 72 h post-transfection, more than 50% reduction was achieved in both Caki-1 and ACHN cells during our experiment window (Fig. 2a)

Summary

Introduction

Cumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer. Small nucleolar RNA host gene 12 (SNHG12) has been increasingly recognized involving in variety of human cancers such as human osteosarcoma cell, nasopharyngeal carcinoma cell, and human endometrial carcinoma. Wang et al demonstrated that long non-coding SNHG12 promoted cell growth and inhibited cell apoptosis via boosting cell cycle progression [18]. Wang et al reported knockdown of SNHG12 inhibited cell growth and induced apoptosis by up-regulating miR-138 in non-small cell lung cancer [21]. Overexpression of SNHG12 contributed multidrug resistance through activating the MAPK/Slug pathway by sponging miR-181a in non-small lung cancer [22].

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