MicroRNA-152 Regulates Endometrial Serous Carcinoma Cell Motility by Suppressing Matrix Metalloproteinase 10 Expression

MicroRNA-152 Regulates Endometrial Serous Carcinoma Cell Motility by Suppressing Matrix Metalloproteinase 10 Expression

Shogo Shigeta,¹ Yoh Watanabe,² Fumihiko Suzuki,^1,3 Satoru Nagase,⁴ Yusuke Shibuya,¹ Masumi Ishibashi,¹ Tomoyuki Nagai,¹ Naomi Shiga,¹ Masafumi Toyoshima,⁵ Hideki Tokunaga,¹ Muneaki Shimada¹ and Nobuo Yaegashi¹

¹Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Miyagi, Japan
²Division of Obstetrics and Gynecology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan
³DNA Chip Research Inc. Tokyo, Japan
⁴Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata, Yamagata, Japan
⁵Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan

MicroRNA-152 (miR-152) expression has been reported to be associated with poor prognosis in patients with endometrial serous carcinoma (ESC). However, the function of miR-152 in ESCs is not fully understood. The present study aimed to investigate the involvement of miR-152 in ESC progression. The influence of miR-152 overexpression on cell proliferation and motility was assessed by transfecting two human ESC cell lines, USPC-1 and SPAC-1-L, with a miR-152 precursor. MiR-152 overexpression increased apoptosis and inhibited the proliferation of the two ESC cell lines. Cell motility was also suppressed in both cell lines following precursor transfection. Conversely, miR-152 inhibitor transfection led to an increase in cell migration ability, suggesting the involvement of miR-152 in ESC cell motility. Results of the analysis of publicly available messenger RNA dataset indicated that high expression of matrix metalloproteinase 10 (MMP10), one of the predicted targets of miR-152 by microRNA target prediction database, was a poor prognostic factor for ESC. In vitro examination results revealed that miR-152 overexpression reduced MMP10 expression, and knockdown of MMP10 significantly reduced cell motility. This study elucidates the function of miR-152 as a tumor suppressor in ESCs. We demonstrated that miR-152 plays an important role in ESC cell motility by regulating MMP10 expression.

Keywords —— cell motility; endometrial neoplasm; matrix metalloproteinase 10; microRNA-152; serous carcinoma

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Tohoku J. Exp. Med 2022, 256, 249-258.

Correspondence: Shogo Shigeta, M.D., Ph.D., Department of Obstetrics and Gynecology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.

e-mail: shogo.shigeta.a4@tohoku.ac.jp