Hsa_circ_0000497 and hsa_circ_0000918 contributed to peritoneal metastasis of ovarian cancer via ascites

Ning Luo; Zubaidan Sulaiman; Chunyan Wang; Jinye Ding; Yingying Chen; Biting Liu; Zhongping Cheng; Shupeng Liu

doi:10.1186/s12967-022-03404-9

Hsa_circ_0000497 and hsa_circ_0000918 contributed to peritoneal metastasis of ovarian cancer via ascites

J Transl Med. 2022 May 10;20(1):201. doi: 10.1186/s12967-022-03404-9.

Authors

Ning Luo^{1

2}, Zubaidan Sulaiman^{1

2}, Chunyan Wang^{1

2}, Jinye Ding^{1

2}, Yingying Chen^{1

2}, Biting Liu^{1

2}, Zhongping Cheng^{3

4}, Shupeng Liu^{5

6

7}

Affiliations

¹ Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
² Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai, 200072, China.
³ Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China. mdcheng18@tongji.edu.cn.
⁴ Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai, 200072, China. mdcheng18@tongji.edu.cn.
⁵ Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China. lshup@tongji.edu.cn.
⁶ Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai, 200072, China. lshup@tongji.edu.cn.
⁷ Department of Obstetrics and Gynecology, Putuo People's Hospital, Tongji University, Shanghai, 200060, China. lshup@tongji.edu.cn.

Abstract

Purpose: As a common complication of epithelial ovarian cancer (EOC), malignant ascites contributes to the peritoneal metastasis of EOC. CircRNAs play essential roles in tumor metastasis. However, no circRNAs have been reported to be involved in EOC peritoneal metastasis via ascites.

Methods: Total of 22 samples from 9 EOC patients containing primary lesions (T), tumor cells from ascites (ASC), and metastatic lesions (M) were included for RNA sequencing to identify differentially expressed circRNAs and mRNAs among different tumors. Bioinformatic analyses, including single-sample Gene Set Enrichment Analysis and soft cluster analysis, were performed to find circRNAs potentially correlated with ascitic metastasis. Wound healing and transwell analysis were performed to evaluate tumor cells metastasis in vitro. Quantitative real-time PCR and western-blot were used for gene expression evaluation.

Results: According to transcriptomic analysis, ASC showed mesenchymal phenotype while T and M showed epithelial phenotype. 10 circRNAs were differentially expressed among ASC, T, and M. Among them, hsa_circ_0000497 and hsa_circ_0000918 were significantly up-regulated in ASC. Functional analysis showed that both hsa_circ_0000497 and hsa_circ_0000918 promoted metastasis of EOC via epithelial-mesenchymal transition (EMT) in vitro. The regulatory network construction identified 8 miRNAs and 19 mRNAs, and 7 miRNAs and 17 mRNAs as potential downstream target genes of hsa_circ_0000497 and hsa_circ_0000918, respectively, which may play pivotal roles in EOC ascitic metastasis.

Conclusions: circRNAs (hsa_circ_0000497 and hsa_circ_0000918) contribute to metastasis of EOC via ascites by regulating EMT. These circRNAs may serve as novel potential therapeutic targets or prognostic biomarkers for EOC peritoneal metastasis.

Keywords: Ascites; Circular RNA; Epithelial-Mesenchymal Transition; Ovarian cancer; Peritoneal metastasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ascites / genetics
Carcinoma, Ovarian Epithelial / genetics
Female
Humans
MicroRNAs* / genetics
MicroRNAs* / metabolism
Ovarian Neoplasms* / genetics
Peritoneal Neoplasms* / genetics
RNA, Circular / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism

Substances

MicroRNAs
RNA, Circular
RNA, Messenger