Yingying Zhou1, Min Wang2, Ting Shuang3, Yisi Liu4, Yongqi Zhang5, Cong Shi6. 1. Department of Obstetrics/Gynecology, Shengjing Hospital, China Medical University, Shenyang, China. 2. Department of Obstetrics/Gynecology, Shengjing Hospital, China Medical University, Shenyang, China. Electronic address: wm21st@126.com. 3. Department of Obstetrics/Gynecology, Shengjing Hospital, China Medical University, Shenyang, China; Department of Obstetrics/Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, China. 4. Department of Obstetrics/Gynecology, Shengjing Hospital, China Medical University, Shenyang, China; Cancer Hospital, China Medical University, Shenyang, China. 5. Department of Obstetrics/Gynecology, Shengjing Hospital, China Medical University, Shenyang, China; Department of Obstetrics/Gynecology, Roicare Hospital & Clinics, Shenyang, China. 6. Department of Obstetrics/Gynecology, Shengjing Hospital, China Medical University, Shenyang, China; Women's and Children's Hospital, Shenyang, China.
Abstract
BACKGROUND: Extended from our previously observation that expression of miR-1307 in chemoresistant primary ovarian cancer tissues is elevated, here we are aiming to dissect the function of miR-1307 and its predicted target gene, CIC (capicua transcriptional repressor), in ovarian cancer chemotherapy. METHODS: We evaluated the expression of miR-1307 and CIC in chemoresistant and chemosensitive ovarian cancer tissues and cells by real time-PCR and western blot. We used chemoresistant/chemosensitive cells with miR-1307 suppression/overexpression to study the biological effects of miR-1307 by MTT and flow cytometer. Dual luciferase reporter gene assay was used to validate direct binding between miR-1307 and the 3'-UTR of CIC. Real-time PCR and western blot analyses, MTT and flow cytometry were used to reveal the biological effects of miR-1307 and CIC, as well as their regulation. RESULTS: We found that miR-1307 affects cell cycle dynamics, cell viability in ovarian cancer cells. In addition, its expression level can influence chemosensitivity to paclitaxel in ovarian cancer cells. We also validate that CIC is a downstream target of miR-1307 via its regulation on 3'-UTR of CIC gene and ETV4 and ETV5 are also regulated by miR-1307/CIC axis. CONCLUSIONS: Our data suggested that miR-1307 may be involved in the resistance of ovarian cancer to chemotherapy drugs via regulation of CIC, and should be further explored as a potential therapeutic target.
BACKGROUND: Extended from our previously observation that expression of miR-1307 in chemoresistant primary ovarian cancer tissues is elevated, here we are aiming to dissect the function of miR-1307 and its predicted target gene, CIC (capicua transcriptional repressor), in ovarian cancer chemotherapy. METHODS: We evaluated the expression of miR-1307 and CIC in chemoresistant and chemosensitive ovarian cancer tissues and cells by real time-PCR and western blot. We used chemoresistant/chemosensitive cells with miR-1307 suppression/overexpression to study the biological effects of miR-1307 by MTT and flow cytometer. Dual luciferase reporter gene assay was used to validate direct binding between miR-1307 and the 3'-UTR of CIC. Real-time PCR and western blot analyses, MTT and flow cytometry were used to reveal the biological effects of miR-1307 and CIC, as well as their regulation. RESULTS: We found that miR-1307 affects cell cycle dynamics, cell viability in ovarian cancer cells. In addition, its expression level can influence chemosensitivity to paclitaxel in ovarian cancer cells. We also validate that CIC is a downstream target of miR-1307 via its regulation on 3'-UTR of CIC gene and ETV4 and ETV5 are also regulated by miR-1307/CIC axis. CONCLUSIONS: Our data suggested that miR-1307 may be involved in the resistance of ovarian cancer to chemotherapy drugs via regulation of CIC, and should be further explored as a potential therapeutic target.
Authors: Pietro Carotenuto; Francesco Amato; Andrea Lampis; Colin Rae; Somaieh Hedayat; Maria C Previdi; Domenico Zito; Maya Raj; Vincenza Guzzardo; Francesco Sclafani; Andrea Lanese; Claudia Parisi; Caterina Vicentini; Ian Said-Huntingford; Jens C Hahne; Albert Hallsworth; Vladimir Kirkin; Kate Young; Ruwaida Begum; Andrew Wotherspoon; Kyriakos Kouvelakis; Sergio Xavier Azevedo; Vasiliki Michalarea; Rosie Upstill-Goddard; Sheela Rao; David Watkins; Naureen Starling; Anguraj Sadanandam; David K Chang; Andrew V Biankin; Nigel B Jamieson; Aldo Scarpa; David Cunningham; Ian Chau; Paul Workman; Matteo Fassan; Nicola Valeri; Chiara Braconi Journal: Nat Commun Date: 2021-11-18 Impact factor: 14.919