Department of Urology, First Hospital of China Medical University, Shenyang, China.
J Cell Mol Med. 2021 May;25(10):4696-4708. doi: 10.1111/jcmm.16417. Epub 2021 Mar 30.
Small nucleolar RNA host gene 12 (SNHG12) has been indicated in the tumorigenesis of various human cancers, including clear cell renal cell carcinoma (ccRCC). However, the underlying mechanisms of SNHG12 driving progression of ccRCC remain incompletely understood. In the present study, we discovered that SNHG12 is up-regulated in ccRCC and that overexpression of SNHG12 predicted poor clinical outcome of ccRCC patients. SNHG12 knockdown notably inhibited proliferation and migration of RCC cells. Furthermore, we discovered that miR-30a-3p, a putative ccRCC inhibitor, was competitively sponged by SNHG12. Via the crosstalk network, SNHG12 was capable of up-regulating multiple target genes of miR-30a-3p, namely, RUNX2, WNT2 and IGF-1R, which have been identified to facilitate tumorigenesis of ccRCC. Taken together, our present study suggested a novel ceRNA network, in which SNHG12 could promote the malignancy of ccRCC although competitively binding with miR-30a-3p and consequently release the expression of its downstream cancer-related genes.
小核仁 RNA 宿主基因 12(SNHG12)已被证实参与多种人类癌症的发生,包括肾透明细胞癌(ccRCC)。然而,SNHG12 驱动 ccRCC 进展的潜在机制尚不完全清楚。在本研究中,我们发现 SNHG12 在 ccRCC 中上调,并且 SNHG12 的过表达预示着 ccRCC 患者的临床预后不良。SNHG12 敲低显著抑制了 RCC 细胞的增殖和迁移。此外,我们发现 miR-30a-3p,一种潜在的 ccRCC 抑制剂,可被 SNHG12 竞争性吸附。通过串扰网络,SNHG12 能够上调 miR-30a-3p 的多个靶基因,即 RUNX2、WNT2 和 IGF-1R,这些基因已被证实促进 ccRCC 的发生。总之,本研究提出了一个新的 ceRNA 网络,其中 SNHG12 可通过竞争性结合 miR-30a-3p 促进 ccRCC 的恶性进展,从而释放其下游与癌症相关的基因表达。