Yu Lan, Li Hui, Li Zhiying, Jia Jianchao, Wu Zhouying, Wang Min, Li Feng, Feng Zongqi, Xia Huilin, Gao Guanxin
Clinical Medical Research Center, Inner Mongolia People's Hospital, Hohhot 010017, People's Republic of China.
Department of Oncology, Inner Mongolia People's Hospital, Hohhot 010017, People's Republic of China.
Onco Targets Ther. 2020 Apr 16;13:3187-3196. doi: 10.2147/OTT.S233256. eCollection 2020.
Long non-coding RNAs (lncRNAs) are regarded as crucial regulators for cancer initiation and progression. Heart and Neural Crest Derivatives Expressed 2 antisense RNA 1 (HAND2-AS1) was recently proposed to function as tumor suppressor in several human cancers. However, its role in gastric cancer (GC) remains unclear.
HAND2-AS1 expression in GC tissues and normal tissues was analyzed at GEPIA (a web server for gene expression profiling analysis). Moreover, RT-qPCR method was utilized to explore HAND2-AS1 expression in GC cells and normal cell. In vitro experiments were carried out using cell counting kit-8 assay, colony formation assay, and flow cytometry assay, respectively. Bioinformatic analysis and luciferase activity reporter assay were performed to identify the downstream targets of HAND2-AS1.
We found HAND2-AS1 has decreased expression in both GC tissues and cells. Overexpression of HAND2-AS1 was able to inhibit GC cell proliferation, colony formation, but promote apoptosis. On the contrary, knockdown of HAND2-AS1 could cause the opposite effects on GC cells. Furthermore, HAND2-AS1 was shown to function as a competitive RNA that binds with microRNA-590-3p (miR-590-3p) to affect the expression of potassium sodium-activated channel subfamily T member 2 (KCNT2).
Our results indicated the tumor suppressive role of HAND2-AS1 in GC. Also, the newly identified HAND2-AS1/miR-590-3p/KCNT2 axis will help us to understand the role of HAND2-AS1 in cancer.
长链非编码RNA(lncRNAs)被认为是癌症发生和发展的关键调节因子。心脏和神经嵴衍生物表达2反义RNA1(HAND2-AS1)最近被认为在几种人类癌症中发挥肿瘤抑制作用。然而,其在胃癌(GC)中的作用仍不清楚。
在GEPIA(一个用于基因表达谱分析的网络服务器)上分析HAND2-AS1在GC组织和正常组织中的表达。此外,利用RT-qPCR方法探索HAND2-AS1在GC细胞和正常细胞中的表达。分别使用细胞计数试剂盒-8检测、集落形成检测和流式细胞术检测进行体外实验。进行生物信息学分析和荧光素酶活性报告基因检测以鉴定HAND2-AS1的下游靶点。
我们发现HAND2-AS1在GC组织和细胞中的表达均降低。HAND2-AS1的过表达能够抑制GC细胞增殖、集落形成,但促进细胞凋亡。相反,敲低HAND2-AS1对GC细胞会产生相反的作用。此外,HAND2-AS1被证明作为一种竞争性RNA与微小RNA-590-3p(miR-590-3p)结合,从而影响钾钠激活通道亚家族T成员2(KCNT2)的表达。
我们的结果表明HAND2-AS1在GC中具有肿瘤抑制作用。此外,新鉴定的HAND2-AS1/miR-590-3p/KCNT2轴将有助于我们理解HAND2-AS1在癌症中的作用。