Estrogen receptor-mediated miR-486-5p regulation of OLFM4 expression in ovarian cancer
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Hanyu Ma1,*, Tian Tian1,*, Shuang Liang1,*, Xubin Liu1, Hongwei Shen2, Meng Xia2, Xingyang Liu2, Wenhui Zhang1, Liantang Wang1, Shangwu Chen3 and Li Yu1
1 Department of Pathology, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China
2 Department of Gynecology and Obstetrics, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China
3 State Key Laboratory for Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen (Zhongshan) University, Guangzhou, China
* These authors have contributed equally to this work
Li Yu, email:
Shangwu Chen, email:
Keywords: OLFM4, ovarian serous adenocarcinoma, estrogen, miR-486-5p
Received: August 19, 2015 Accepted: January 27, 2016 Published: February 07, 2016
Estrogen signaling influences the development and progression of ovarian tumors, but the underlying mechanisms are not well understood. In a previous study we demonstrated that impairment of estrogen receptor alpha (ERα)-mediated olfactomedin 4 (OLFM4) expression promotes the malignant progression of endometrioid adenocarcinoma, and we identified OLFM4 as a potential target of miR-486-5p. In this study we investigated the role of OLFM4 in ovarian serous adenocarcinoma. Ovarian serous adenocarcinoma tissues had reduced OLFM4 expression. Expression of OLFM4 was positively correlated with ERα expression, and estrogen (E2) treatment in ovarian cancer cells induced OLFM4 expression in an ERα-dependent manner. In contrast to ERα, miR-486-5p levels were inversely correlated with OLFM4 expression in ovarian serous adenocarcinoma. Ovarian cancer cells transfected with miR-486-5p mimics showed decreased OLFM4 mRNA expression, and ovarian cancer cells treated with E2 showed reduced cellular miR-486-5p levels. OLFM4 knockdown enhanced proliferation, migration, and invasion by ovarian cancer cells. Low expression of OLFM4 was also associated with high tumor FIGO stage and poor tumor differentiation. These results suggest OLFM4 is downregulated by miR-486-5p, which contributes to ovarian cancer tumorigenesis. Conversely, estrogen receptor signaling downregulates miR-486-5p and upregulates OLFM4 expression, slowing the development and progression of ovarian cancer.
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