miR-191 Modulates Malignant Transformation of Endometriosis Through Regulating TIMP3

BACKGROUND Although aberrant expression of several miRNAs was found during the pathological development of endometriosis to endometriosis-associated ovarian cancer (EAOC), their roles are not fully understood. miR-191 is a miRNA significantly upregulated in endometriosis and EAOC patients. However, its downstream network is still not clear. This study explored its role in malignant transformation of endometriosis to EAOC. MATERIAL AND METHODS Tissues from 12 healthy controls, 12 patients with endometriomas, and 12 patients with EAOC were used to verify miR-191 expression by using qRT-PCR. Endometriosis cell line CRL-7566 and ovarian endometrioid carcinoma cell line CRL-11731 were used to explore the downstream regulative function of miR-191. RESULTS By using tissue and serum samples from healthy, endometriosis, and EAOC participants, we confirmed that miR-191 expression was significantly higher in endometriosis and EAOC participants. Interestingly, we also observed that TIMP3 expression was negatively correlated with miR-191 expression. Overexpressing miR-191 in CRL-7566 significantly increased cell proliferation and invasion, while miR-191 knockdown in CRL-11731 cells significantly decreased cell proliferation and invasion. These modulating effects of miR-191 are achieved through its regulation of TIMP3. CONCLUSIONS miR-191 can directly regulate TIMP3 expression, thereby affecting cell proliferation rate and invasion ability. The miR-191-TIMP3 axis might be critical in the malignant transformation of endometriosis to EAOC.