LncRNA CACS15 accelerates the malignant progression of ovarian cancer through stimulating EZH2-induced inhibition of APC

Yanhong Liu; Jin Sun; Jinyong Yu; Wei Ge; Xiaoguang Xiao; Senge Dai; Qiyun Xiang

LncRNA CACS15 accelerates the malignant progression of ovarian cancer through stimulating EZH2-induced inhibition of APC

Am J Transl Res. 2019 Oct 15;11(10):6561-6568. eCollection 2019.

Authors

Yanhong Liu¹, Jin Sun², Jinyong Yu³, Wei Ge⁴, Xiaoguang Xiao⁵, Senge Dai⁶, Qiyun Xiang⁷

Affiliations

¹ Department of Obstetrics and Gynecology, The Second Hospital of Shandong University Jinan 250033, Shangdong Province, China.
² Department of Obstetrics and Gynecology, The General Hospital of Western Theater Command Chengdu 610083, Sichuan Province, China.
³ Department of Anesthesiology, Zhucheng Maternal and Child Health Hospital Zhucheng 262200, Shangdong Province, China.
⁴ Department of Oncology, Renmin Hospital of Wuhan University Wuhan 430000, Hubei Province, China.
⁵ Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology Wuhan 430030, Hubei Province, China.
⁶ Department of Obstetrics and Gynecology, Zhejiang Provincial Integrated Chinese and Western Medicine Hospital Hangzhou 310003, Zhejiang Province, China.
⁷ Department of Laboratory, The Third People's Hospital Yichang 443000, Hubei Province, China.

PMID: 31737207
PMCID: PMC6834498

Abstract

To elucidate the potential function of lncRNA CACS15 in the progression of ovarian cancer (OC) and its underlying mechanism. CACS15 level in OC tissues and cell lines was determined by qRT-PCR. Correlation between CACS15 level and survival of OC patients was analyzed through Kaplan-Meier method. Regulatory effects of CACS15 on cellular behaviors of OC cells were evaluated through CCK-8 and Transwell assay. Subsequently, RIP and RNA pull-down were performed to uncover the interaction between CACS15 and EZH2. Through ChIP assay, the interaction between EZH2 and APC was illustrated. A series of rescue experiments were finally conducted to elucidate the role of CACS15/APC axis in the malignant progression of OC. CACS15 was upregulated in OC tissues and cell lines relative to matched ones. High-level of CACS15 predicted worse survival in OC patients. Knockdown of CACS15 attenuated proliferative, migratory and invasive abilities of OC cells. CACS15 was mainly distributed in cytoplasm of OC cells, which was interacted with EZH2 at post-transcriptional level. Knockdown of CACS15 reduced the occupancies of EZH2 and H3K27me3 in APC promoter regions. Notably, knockdown of APC could reverse the regulatory effect of CACS15 on cellular behaviors of OC cells. LncRNA CACS15 inhibits the expression of APC by recruiting EZH2, thus accelerating the progression of ovarian cancer as an oncogene.

Keywords: APC; EZH2; LncRNA CACS15; Ovarian cancer; metastasis.