Lunhua Shen1,2, Jiafeng Dang3, Shengfeng Liu1, Biao Xian4, Yan Deng5, Dacheng Qu6,7. 1. 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. 2. 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. 3. Department of Obstetrics and Gynecology, Pidu District People's Hospital, Chengdu City, Sichuan Province, China. 4. Department of Clinical Medicine, North Sichuan Medical College, Nanchong City, Sichuan Province, China. 5. Department of Obstetrics and Gynecology, People's Hospital of Lezhi County, Sichuan Province, Ziyang City, Sichuan Province, China. 6. 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. qdacheng21@126.com. 7. 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. qdacheng21@126.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Circ_VPRBP inhibited cell proliferation, migration and invasion and promoted cell apoptosis of cervical cancer cells by regulating miR-93-5p/FRMD6 axis.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Circ_VPRBP inhibited cell proliferation, migration and invasion and promoted cell apoptosis of cervical cancer cells by regulating miR-93-5p/FRMD6 axis.