miR-652 Promotes Tumor Proliferation and Metastasis by Targeting RORA in Endometrial Cancer.

Abstract

Endometrial cancer is the most common gynecologic malignancy, whose incidence rate is on the rise. However, the underlying mechanisms of endometrial cancer are not very clear yet. miRNAs have been considered to be playing important roles in malignant behavior. Here, miR-652 was significantly upregulated in endometrial cancer, which correlated with shorter overall survival and earlier recurrence. Moreover, overexpression of miR-652 in endometrial cancer cells promoted proliferation, migration, and invasion in vitro and facilitated tumor growth and metastasis in vivo. In contrast, downregulation of miR-652 in endometrial cancer cells inhibited these processes both in vitro and in vivo. Mechanistically, miR-652 promotes proliferation and metastasis through directly targeting RORA. Both mRNA and protein level of RORA were negatively related with miR-652 and overexpression of RORA can rescue the promotion effect of miR-652. Further experiments indicated miR-652 overexpression can activate the Wnt/β-catenin pathway and RORA can downregulate β-catenin and function as a tumor suppressor in endometrial cancer. Collectively, these findings demonstrate that miR-652 functions as an oncomir in endometrial cancer. IMPLICATIONS: This study suggests that the miR-652 is a critical regulator of proliferation and metastasis in endometrial cancer and may serve as a therapeutic target.

• Authors: Xiaomei Sun, Samina Dongol, Chunping Qiu, Ying Xu, Chenggong Sun, Zhiwei Zhang, Xingsheng Yang, Qing Zhang, Beihua Kong
• Journal: Molecular cancer research : MCR (Mol Cancer Res) Vol. 16 Issue 12 Pg. 1927-1939 (12 2018) ISSN: 1557-3125 [Electronic] United States
• PMID: 30093563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2018 American Association for Cancer Research.

Chemical References

• MIRN652 microRNA, human
• MicroRNAs
• Nuclear Receptor Subfamily 1, Group F, Member 1
• RORA protein, human

Topics

• Animals
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Endometrial Neoplasms (genetics, metabolism, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• MicroRNAs (genetics)
• Neoplasm Metastasis
• Neoplasm Transplantation
• Nuclear Receptor Subfamily 1, Group F, Member 1 (genetics, metabolism)
• Prognosis
• Survival Analysis
• Up-Regulation
• Wnt Signaling Pathway