Zhang Furui, Cheng Ruirui, Li Ping, Lu Chunya, Zhang Guojun
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou, 450052, China.
Cancer Cell Int. 2021 Jan 25;21(1):73. doi: 10.1186/s12935-021-01764-8.
Non-small cell lung cancer (NSCLC) is a threat to human health. Circular RNAs (circRNAs) have been proved to function in NSCLC development. In this study, the role of circRNA hsa_circ_0010235 in NSCLC progression and the possible molecular mechanism were explored.
Expression of hsa_circ_0010235, miRNA (miR)-433-3p and TOR signaling pathway regulator-like (TIPRL) was examined by quantitative real-time PCR (qRT-PCR). Cell viability and clonogenicity were detected by cell counting kit-8 (CCK-8) assay and colony formation assay, respectively. Flow cytometry was performed to monitor cell apoptosis and cell cycle distribution. Western blot assay was employed to evaluate the protein levels of TIPRL, light chain 3 (LC3)-II/I and p62. Cell metastasis was assessed by Transwell and wound healing assays. The targeted relationship between miR-433-3p and hsa_circ_0010235 or TIPRL was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Furthermore, the role of hsa_circ_0010235 in vivo was investigated by xenograft assay.
Hsa_circ_0010235 and TIPRL were highly expressed in NSCLC tissues and cells, while miR-433-3p was downregulated. Depletion of hsa_circ_0010235 or gain of miR-433-3p repressed proliferation and autophagy but promoted apoptosis in NSCLC cells. Hsa_circ_0010235 sponged miR-433-3p to upregulate TIPRL expression, so as to affect NSCLC development. Hsa_circ_0010235 knockdown also blocked tumor growth in vivo.
Hsa_circ_0010235 knockdown suppressed NSCLC progression by regulating miR-433-3p/TIPRL axis, affording a novel mechanism of NSCLC progression.
非小细胞肺癌（NSCLC）对人类健康构成威胁。环状RNA（circRNA）已被证明在NSCLC发展中发挥作用。在本研究中，探讨了circRNA hsa_circ_0010235在NSCLC进展中的作用及可能的分子机制。
通过定量实时PCR（qRT-PCR）检测hsa_circ_0010235、微小RNA（miR）-433-3p和TOR信号通路调节样蛋白（TIPRL）的表达。分别采用细胞计数试剂盒-8（CCK-8）法和集落形成试验检测细胞活力和克隆形成能力。通过流式细胞术监测细胞凋亡和细胞周期分布。采用蛋白质免疫印迹法评估TIPRL、轻链3（LC3）-II/I和p62的蛋白水平。通过Transwell和伤口愈合试验评估细胞转移情况。通过双荧光素酶报告基因和RNA免疫沉淀（RIP）试验证实miR-433-3p与hsa_circ_0010235或TIPRL之间的靶向关系。此外，通过异种移植试验研究hsa_circ_0010235在体内的作用。
hsa_circ_0010235和TIPRL在NSCLC组织和细胞中高表达，而miR-433-3p表达下调。敲低hsa_circ_0010235或上调miR-433-3P可抑制NSCLC细胞的增殖和自噬，但促进其凋亡。hsa_circ_0010235通过海绵吸附miR-433-3p上调TIPRL表达，从而影响NSCLC的发展。敲低hsa_circ_0010235也可抑制体内肿瘤生长。
敲低hsa_circ_0010235通过调节miR-433-3p/TIPRL轴抑制NSCLC进展，为NSCLC进展提供了一种新机制。
