PMID- 30266988 OWN - NLM STAT- MEDLINE DCOM- 20190301 LR - 20200225 IS - 1476-5594 (Electronic) IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 38 IP - 9 DP - 2019 Feb TI - The interaction of Lin28A/Rho associated coiled-coil containing protein kinase2 accelerates the malignancy of ovarian cancer. PG - 1381-1397 LID - 10.1038/s41388-018-0512-9 [doi] AB - Ovarian cancer (OC) is the leading cause of death among women with gynecologic malignant diseases, however, the molecular mechanism of ovarian cancer is not well defined. Previous studies have found that RNA binding protein Lin28A is a key factor of maintain the pluripotency of stem cells, and it is positively correlated with the degree of several cancers (breast, prostate, liver cancer, etc). Our previous study shows that Lin28A is highly expressed in OC tissues and is involved in the regulation of OC cell biological behavior. In this study, we confirmed that high expression of Lin28A promoted the survival, invasion, metastasis, and inhibited the apoptosis of OC cells. Lin28A interacts with Rho associated coiled-coil containing protein kinase2 (ROCK2) but not ROCK1 and upregulates the expression of ROCK2 in OC cells. The binding sites of each other were identified by truncated mutations and Immuno-precipitaion (IP) assay. After knock down of ROCK2 in cells with high expression of Lin28A, the survival, invasion, metastasis was significantly inhibited and early apoptosis was increased in OC cells and OC xenograft in nude mice. Our experimental data also showed that knock down of ROCK2 but not ROCK1 inhibited the invasion by decreasing the expression of N-cadherin, Slug, beta-catenin and increasing ZO-1 expression. Simultaneously, knock down of ROCK2 induced cell apoptosis by increasing cleaved Caspase-9,cleaved Caspase-7, and cleaved Caspase-3. Taken together, Lin28A regulated the biological behaviors in OC cells through ROCK2 and the interaction of Lin28A/ROCK2 may be a new target for diagnosis and gene therapy of OC. FAU - Zhong, Yancheng AU - Zhong Y AD - Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, China. FAU - Yang, Sheng AU - Yang S AD - Human Reproduction Center, Shenzhen Hospital of Hongkong University, Haiyuan 1 Road, Futian, Shenzhen, China. FAU - Wang, Wei AU - Wang W AD - The Pathology Department of the Jining Medical University, Shan Dong, China. FAU - Wei, Pingpin AU - Wei P AD - Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, China. FAU - He, Shiwei AU - He S AD - Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, China. FAU - Ma, Haotian AU - Ma H AD - Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, China. FAU - Yang, Juan AU - Yang J AD - Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, China. FAU - Wang, Qian AU - Wang Q AD - The department of Gynecology of Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Cao, Lanqin AU - Cao L AD - The department of Gynecology of Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Xiong, Wei AU - Xiong W AD - Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, China. FAU - Zhou, Ming AU - Zhou M AD - Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, China. FAU - Li, Guiyuan AU - Li G AD - Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, China. FAU - Shuai, Cijun AU - Shuai C AD - Jiangxi University of Science and Technology, Ganzhou, 341000, China. FAU - Peng, Shuping AU - Peng S AD - Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, China. shuping@csu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180928 PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (LIN28B protein, human) RN - 0 (RNA-Binding Proteins) RN - EC 2.7.11.1 (rho-Associated Kinases) RN - EC 3.4.22.- (Caspases) SB - IM MH - Animals MH - Apoptosis/genetics MH - Carcinogenesis/*genetics MH - Caspases/genetics MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Mice MH - Neoplasm Invasiveness/genetics/pathology MH - Ovarian Neoplasms/*genetics/pathology MH - RNA-Binding Proteins/*genetics MH - Xenograft Model Antitumor Assays MH - rho-Associated Kinases/*genetics PMC - PMC6372474 COIS- The authors declare that they have no conflict of interest. EDAT- 2018/09/30 06:00 MHDA- 2019/03/02 06:00 PMCR- 2018/09/28 CRDT- 2018/09/30 06:00 PHST- 2018/03/04 00:00 [received] PHST- 2018/09/03 00:00 [accepted] PHST- 2018/08/04 00:00 [revised] PHST- 2018/09/30 06:00 [pubmed] PHST- 2019/03/02 06:00 [medline] PHST- 2018/09/30 06:00 [entrez] PHST- 2018/09/28 00:00 [pmc-release] AID - 10.1038/s41388-018-0512-9 [pii] AID - 512 [pii] AID - 10.1038/s41388-018-0512-9 [doi] PST - ppublish SO - Oncogene. 2019 Feb;38(9):1381-1397. doi: 10.1038/s41388-018-0512-9. Epub 2018 Sep 28.