Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College, No. 1, Maoyuan South Road, Shunqing District, Nanchong City, 637000, Sichuan Province, China.
Non-Invasive and Microinvasive Laboratory of Gynecology, Affiliated Hospital of North Sichuan Medical College, No. 1, Maoyuan South Road, Shunqing District, Nanchong City, 637000, Sichuan Province, China.
Reprod Sci. 2022 Aug;29(8):2251-2264. doi: 10.1007/s43032-022-00923-0. Epub 2022 May 2.
Cervical cancer is a malignant tumor that threatens the life and health of women. Circular RNA (circRNA) is a research hotspot in human diseases including cervical cancer. However, the research of circRNA viral protein R-binding protein (circ_VPRBP) in cervical cancer is blank.
Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of target genes in cervical cancer tissues and cells. The expression of related proteins was detected by western blot. The localization of circ_VPRBP was detected by nuclear cytoplasmic separation, and the stability of circ_VPRBP was verified by actinomycin D. After transfection with oligonucleotides and/or plasmids, cell proliferation, migration, invasion and apoptosis were detected by 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, or flow cytometry assays. Mechanistically, the interaction between microRNA-93-5p (miR-93-5p) and circ_VPRBP/FERM domain containing 6 (FRMD6) was verified by dual luciferase reporter assay. Animal experiment was conducted to investigate the role of circ_VPRBP in vivo.
Circ_VPRBP was down-regulated in cervical cancer tissues and cells, and overexpression of circ_VPRBP inhibited proliferation and promoted apoptosis of Caski and C33A cells. MiR-93-5p was a target of circ_VPRBP, and miR-93-5p mimic reversed the effect of circ_VPRBP on cell behavior. FRMD6 was a downstream target of miR-93-5p, and down-regulated FRMD6 reversed the cell viability, migration and invasion of cervical cancer cells inhibited by anti-miR-93-5p. Circ_VPRBP inhibited tumor growth by regulating miR-93-5p and FRMD6 in vivo.
Circ_VPRBP inhibited cell proliferation, migration and invasion and promoted cell apoptosis of cervical cancer cells by regulating miR-93-5p/FRMD6 axis.
宫颈癌是一种威胁女性生命健康的恶性肿瘤。环状 RNA（circRNA）是包括宫颈癌在内的人类疾病的研究热点。然而，环状 RNA 病毒蛋白 R 结合蛋白（circ_VPRBP）在宫颈癌中的研究尚属空白。
采用实时定量聚合酶链反应（RT-qPCR）检测宫颈癌组织和细胞中靶基因的表达，采用 Western blot 检测相关蛋白的表达，采用核质分离检测 circ_VPRBP 的定位，采用放线菌素 D 验证 circ_VPRBP 的稳定性。转染寡核苷酸和/或质粒后，通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2-H-四唑溴盐（MTT）、集落形成、5-乙炔基-2'-脱氧尿苷（EdU）、Transwell 或流式细胞术检测细胞增殖、迁移、侵袭和凋亡。通过双荧光素酶报告基因检测验证 microRNA-93-5p（miR-93-5p）与 circ_VPRBP/含 FERM 结构域蛋白 6（FRMD6）之间的相互作用。通过动物实验研究 circ_VPRBP 在体内的作用。
circ_VPRBP 在宫颈癌组织和细胞中下调，过表达 circ_VPRBP 抑制 Caski 和 C33A 细胞的增殖并促进其凋亡。miR-93-5p 是 circ_VPRBP 的靶基因，miR-93-5p 模拟物逆转了 circ_VPRBP 对细胞行为的影响。FRMD6 是 miR-93-5p 的下游靶基因，下调 FRMD6 逆转了抗 miR-93-5p 抑制的宫颈癌细胞的细胞活力、迁移和侵袭。circ_VPRBP 通过体内调节 miR-93-5p 和 FRMD6 抑制肿瘤生长。
circ_VPRBP 通过调节 miR-93-5p/FRMD6 轴抑制宫颈癌细胞的增殖、迁移和侵袭，促进其凋亡。
