title: Estrogen receptor-mediated miR-486-5p regulation of OLFM4 expression in ovarian cancer.
abstract: 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.
authors: Department of Pathology, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China.
authors: Hanyu
authors: H
authors: Ma
authors: Department of Pathology, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China.
authors: Tian
authors: T
authors: Tian
authors: Department of Pathology, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China.
authors: Shuang
authors: S
authors: Liang
authors: Department of Pathology, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China.
authors: Xubin
authors: X
authors: Liu
authors: Department of Gynecology and Obstetrics, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China.
authors: Hongwei
authors: H
authors: Shen
authors: Department of Gynecology and Obstetrics, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China.
authors: Meng
authors: M
authors: Xia
authors: Department of Gynecology and Obstetrics, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China.
authors: Xingyang
authors: X
authors: Liu
authors: Department of Pathology, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China.
authors: Wenhui
authors: W
authors: Zhang
authors: Department of Pathology, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China.
authors: Liantang
authors: L
authors: Wang
authors: 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.
authors: Shangwu
authors: S
authors: Chen
authors: Department of Pathology, The First Afﬁliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, China.
authors: Li
authors: L
authors: Yu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; C560945:MIRN486 microRNA, human; D035683:MicroRNAs; C454127:OLFM4 protein, human; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor
keywords: OLFM4; estrogen; miR-486-5p; ovarian serous adenocarcinoma