Jin Jiongwei, Xu Botao, Hu Zhiyuan, He Xiangfeng
Department of Cardiothoracic Surgery, Zhuji People's Hospital, Shaoxing University, Zhuji, China.
Transl Cancer Res. 2022 Jan;11(1):242-251. doi: 10.21037/tcr-21-2836.
Circular RNAs (circRNAs) have been confirmed to exert important roles in promoting tumor initiation and progression. However, the expression, effect, and underlying mechanism of circTADA2A in non-small cell lung cancer (NSCLC) remain unclear.
A total of 60 paired clinical samples of NSCLC tissues and corresponding normal adjacent tissues were obtained. Quantitative real-time PCR was used to verify circTADA2A, miR-450b-3p, and HMGN5 mRNA expression. The NSCLC cell Lines A549 and H1299 were individually transfected with circTADA2A and HMGN5. The regulatory interaction between circTADA2A and miR-450b-3p was investigated by dual-luciferase reporter assay. HMGN5 protein expression was detected by Western blotting.
CircTADA2A expression was significantly upregulated and correlated with poor overall survival of NSCLC patients. Functionally, circTADA2A inhibition successfully suppressed the proliferation, invasion, and migration of A549 and H1299 cells. circTADA2A functioned as a competing endogenous RNA to sponge miR-450b-3p to promote the expression of HMGN5 mRNA and protein. Furthermore, a positive relationship between circTADA2A and HMGN5 existed in NSCLC tissues. There were negative relationships between circTADA2A and miR-450b-3p as well as miR-450b-3p and HMGN5 in NSCLC tissues.
These findings suggest that circTADA2A might act as an oncogenic circRNA that promotes NSCLC progression by sponging miR-450b-3p and promoting HMGN5 expression, indicating that the suppression of circTADA2A could become a potential therapeutic target for restraining NSCLC.
环状RNA(circRNAs)已被证实对肿瘤的起始和进展具有重要作用。然而,circTADA2A在非小细胞肺癌(NSCLC)中的表达、作用及潜在机制仍不清楚。
共获取60对NSCLC组织及其相应的癌旁正常组织临床样本。采用定量实时PCR验证circTADA2A、miR-450b-3p和HMGN5 mRNA的表达。分别用circTADA2A和HMGN5转染NSCLC细胞系A549和H1299。通过双荧光素酶报告基因检测法研究circTADA2A与miR-450b-3p之间的调控相互作用。采用蛋白质印迹法检测HMGN5蛋白表达。
circTADA2A表达显著上调,且与NSCLC患者的总生存期较差相关。在功能上,circTADA2A抑制成功抑制了A549和H1299细胞的增殖、侵袭和迁移。circTADA2A作为一种竞争性内源RNA,通过吸附miR-450b-3p来促进HMGN5 mRNA和蛋白的表达。此外,NSCLC组织中circTADA2A与HMGN5之间存在正相关关系。NSCLC组织中circTADA2A与miR-450b-3p以及miR-450b-3p与HMGN5之间均存在负相关关系。
这些发现表明,circTADA2A可能作为一种致癌性circRNA,通过吸附miR-450b-3p并促进HMGN5表达来促进NSCLC进展,提示抑制circTADA2A可能成为抑制NSCLC的潜在治疗靶点。