Li Wen-Zhi, Zou Yun, Song Zheng-Yu, Wei Zi-Wei, Chen Gang, Cai Qi-Liang, Wang Zhong
Department of Urology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University Shanghai 200011, China.
Department of Urology, Jinshan Hospital, Fudan University Shanghai 201508, China.
Am J Transl Res. 2020 Feb 15;12(2):697-707. eCollection 2020.
Non-coding RNA dysregulation is associated with many human diseases, including cancer. This study explored the effects of lncRNA SNHG5 on clear cell renal cell carcinoma (ccRCC). We found that lncRNA SNHG5 is upregulated in human ccRCC tissues and that lncRNA SNHG5 inhibition reduced ccRCC cell invasion and promoted apoptosis . Bioinformatics database searching revealed that lncRNA SNHG5 is predicted to regulate the interaction between miR-363-3p and Twist1. We further verified a ccRCC biomarker panel, which consists of lncRNA SNHG5, miR-363-3p, and Twist1 in ccRCC tissue samples. The direct SNHG5-miR-363-3p and Twist1-miR-363-3p interactions were confirmed via dual-luciferase reporter assays. Additionally, functional assays demonstrated that SNHG5 promotes cell invasion and inhibits apoptosis, while miR-363-3p inhibits cell invasion and promotes apoptosis via an interaction with Twist1. Furthermore, we found that Twist1 promotes tumor metastasis by regulating matrix metalloproteinase (MMP)2 and MMP9 levels. Together, these results suggest that lncRNA SNHG5 may predict ccRCC patient clinical outcome and serve as a novel anti-ccRCC therapeutic target.
非编码RNA失调与包括癌症在内的许多人类疾病相关。本研究探讨了lncRNA SNHG5对肾透明细胞癌（ccRCC）的影响。我们发现lncRNA SNHG5在人类ccRCC组织中上调，并且lncRNA SNHG5抑制可减少ccRCC细胞侵袭并促进细胞凋亡。生物信息学数据库搜索显示，预测lncRNA SNHG5可调节miR - 363 - 3p与Twist1之间的相互作用。我们进一步在ccRCC组织样本中验证了由lncRNA SNHG5、miR - 363 - 3p和Twist1组成的ccRCC生物标志物组。通过双荧光素酶报告基因检测证实了SNHG5与miR - 363 - 3p以及Twist1与miR - 363 - 3p之间的直接相互作用。此外，功能分析表明，SNHG5促进细胞侵袭并抑制细胞凋亡，而miR - 363 - 3p通过与Twist1相互作用抑制细胞侵袭并促进细胞凋亡。此外，我们发现Twist1通过调节基质金属蛋白酶（MMP）2和MMP9水平促进肿瘤转移。总之，这些结果表明lncRNA SNHG5可能预测ccRCC患者的临床结局，并可作为一种新型的抗ccRCC治疗靶点。
