Department of Thoracic Surgery, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China.
Thorac Cancer. 2022 Jun;13(11):1597-1610. doi: 10.1111/1759-7714.14426. Epub 2022 Apr 21.
Circular RNAs (circRNAs) participate in the occurrence and progression of many cancers. CircRNA ataxin 7 (circATXN7) (circBase ID: hsa_circ_0066436) plays a promoting influence on gastric cancer progression. However, the biological role of circATXN7 in non-small cell lung cancer (NSCLC) is indistinct.
Levels of circATXN7, microRNA (miR)-7-5p, and profilin 2 (PFN2) mRNA were detected using quantitative real-time polymerase chain reaction (RT-qPCR). Proliferation, apoptosis, metastasis, and invasion were analyzed using cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays. Protein levels were analyzed using western blotting (WB) and immunohistochemistry (IHC). The relationship between circATXN7 or PFN2 and miR-7-5p was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The biological function of circATXN7 was verified by xenograft assay.
CircATXN7 and PFN2 were highly expressed in NSCLC, whereas miR-7-5p expression had the opposite trend. CircATXN7 overexpression constrained apoptosis and promoted proliferation, metastasis, invasion, and epithelial-mesenchymal transition of NSCLC cells, but circATXN7 silencing played the opposing influence and repressed xenograft tumor growth in vivo. CircATXN7 served as a miR-7-5p sponge, and circATXN7 regulated malignant behaviors of NSCLC cells through sponging miR-7-5p. PFN2 acted as a miR-7-5p target. PFN2 silencing overturned the promoting effect of miR-7-5p inhibitor on NSCLC cell malignancy, while PFN2 overexpression reversed the inhibitory impact of miR-7-5p mimic on NSCLC cell malignancy.
CircATXN7 accelerated the malignancy of NSCLC cells through adsorbing miR-7-5p and upregulating PFN2, offering evidence to support circATXN7 as a target for NSCLC treatment.
环状 RNA（circRNAs）参与了许多癌症的发生和发展。环状 RNA 共济失调蛋白 7（circATXN7）（circBase ID：hsa_circ_0066436）对胃癌的进展起着促进作用。然而，circATXN7 在非小细胞肺癌（NSCLC）中的生物学作用尚不清楚。
采用实时定量聚合酶链反应（RT-qPCR）检测 circATXN7、微小 RNA（miR）-7-5p 和丝切蛋白 2（PFN2）mRNA 的水平。采用细胞计数试剂盒-8（CCK-8）、集落形成、5-乙炔基-2'-脱氧尿苷（EdU）、流式细胞术和 Transwell 检测分析细胞增殖、凋亡、转移和侵袭。采用蛋白质印迹（WB）和免疫组化（IHC）分析蛋白水平。通过双荧光素酶报告和 RNA 免疫沉淀（RIP）检测分析 circATXN7 或 PFN2 与 miR-7-5p 的关系。通过异种移植实验验证 circATXN7 的生物学功能。
circATXN7 和 PFN2 在 NSCLC 中高表达，而 miR-7-5p 的表达呈相反趋势。circATXN7 过表达抑制凋亡并促进 NSCLC 细胞的增殖、转移、侵袭和上皮-间充质转化，但 circATXN7 沉默则发挥相反作用并抑制体内异种移植肿瘤的生长。circATXN7 作为 miR-7-5p 的海绵，通过海绵吸附 miR-7-5p 调节 NSCLC 细胞的恶性行为。PFN2 是 miR-7-5p 的靶基因。PFN2 沉默逆转了 miR-7-5p 抑制剂对 NSCLC 细胞恶性的促进作用，而 PFN2 过表达则逆转了 miR-7-5p 模拟物对 NSCLC 细胞恶性的抑制作用。
circATXN7 通过吸附 miR-7-5p 并上调 PFN2 加速 NSCLC 细胞的恶性转化，为 circATXN7 作为 NSCLC 治疗靶点提供了依据。
