Department of Thoracic Surgery, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yungang District, Guiyang, 550004, Guizhou, China.
Lung. 2022 Feb;200(1):107-117. doi: 10.1007/s00408-021-00500-3. Epub 2022 Jan 11.
Circular RNA migration and invasion inhibitory protein (circMIIP) is reported to be upregulated in non-small cell lung cancer (NSCLC) tissues compared with normal tissues. However, the role and working mechanism of circMIIP in NSCLC progression remain largely unclear.
Cell proliferation ability was analyzed by colony formation assay, cell counting kit-8 (CCK-8) assay, and 5-ethynyl-2'-deoxyuridine assay. Cell apoptosis was assessed by flow cytometry. Transwell assays were performed to analyze the migration and invasion abilities of NSCLC cells. The interaction between microRNA-766-5p (miR-766-5p) and circMIIP or family with sequence similarity 83A (FAM83A) was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. Xenograft tumor model was established to analyze the role of circMIIP on tumor growth in vivo.
CircMIIP was highly expressed in NSCLC tissues and cell lines. CircMIIP knockdown restrained the proliferation, migration and invasion and induced the apoptosis of NSCLC cells. CircMIIP acted as a molecular sponge for miR-766-5p, and circMIIP silencing-mediated anti-tumor effects were largely overturned by the knockdown of miR-766-5p in NSCLC cells. miR-766-5p interacted with the 3' untranslated region (3'UTR) of FAM83A, and FAM83A overexpression largely reversed miR-766-5p accumulation-induced anti-tumor effects in NSCLC cells. CircMIIP competitively bound to miR-766-5p to elevate the expression of FAM83A in NSCLC cells. CircMIIP knockdown significantly restrained xenograft tumor growth in vivo.
CircMIIP promoted cell proliferation, migration and invasion and suppressed cell apoptosis in NSCLC cells through mediating miR-766-5p/FAM83A axis.
据报道，环状 RNA 迁移和入侵抑制蛋白（circMIIP）在非小细胞肺癌（NSCLC）组织中的表达高于正常组织。然而，circMIIP 在 NSCLC 进展中的作用和工作机制在很大程度上仍不清楚。
通过集落形成实验、细胞计数试剂盒-8（CCK-8）实验和 5-乙炔基-2'-脱氧尿苷实验分析细胞增殖能力。通过流式细胞术评估细胞凋亡。通过 Transwell 实验分析 NSCLC 细胞的迁移和侵袭能力。通过双荧光素酶报告实验和 RNA 免疫沉淀实验验证 microRNA-766-5p（miR-766-5p）与 circMIIP 或家族与序列相似性 83A（FAM83A）之间的相互作用。建立异种移植肿瘤模型分析 circMIIP 对体内肿瘤生长的作用。
circMIIP 在 NSCLC 组织和细胞系中高表达。circMIIP 敲低抑制 NSCLC 细胞的增殖、迁移和侵袭，并诱导细胞凋亡。circMIIP 作为 miR-766-5p 的分子海绵，而在 NSCLC 细胞中敲低 miR-766-5p 则大大逆转了 circMIIP 沉默介导的抗肿瘤作用。miR-766-5p 与 FAM83A 的 3'非翻译区（3'UTR）相互作用，FAM83A 过表达在 NSCLC 细胞中显著逆转了 miR-766-5p 积累诱导的抗肿瘤作用。circMIIP 竞争性结合 miR-766-5p 以提高 NSCLC 细胞中 FAM83A 的表达。circMIIP 敲低显著抑制体内异种移植肿瘤的生长。
circMIIP 通过介导 miR-766-5p/FAM83A 轴促进 NSCLC 细胞的增殖、迁移和侵袭，抑制细胞凋亡。
