4.0 Article

MicroRNA-16 represses granulosa cell proliferation in polycystic ovarian syndrome through inhibition of the PI3K/Akt pathway by downregulation of Apelin13

Journal

HUMAN FERTILITY
Volume 26, Issue 3, Pages 611-621

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/14647273.2021.1998661

Keywords

Polycystic ovarian syndrome; granulosa cell; MicroRNA-16; Apelin13

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This study aimed to investigate the specific role of miR-16 in granulosa cell function in PCOS. The results showed that overexpression of miR-16 or knockdown of Apelin13 could suppress granulosa cell proliferation and enhance apoptosis. Additionally, Apelin13 was identified as a potential target of miR-16. Overexpression of Apelin13 could partially reverse the effects of miR-16 overexpression on granulosa cell proliferation and apoptosis. Moreover, inhibiting Apelin13 could suppress granulosa cell proliferation and block the PI3K/Akt pathway.
This study aimed to uncover the specific role of micro RNA-16 (miR-16) in granulosa cell function in polycystic ovarian syndrome (PCOS). After sample collection, the expression levels of miR-16 and Apelin13 in the granulosa cells of PCOS patients and controls were determined. Subsequently, miR-16 mimic, miR-16 inhibitor, pcDNA3.1-Apelin13, sh-Apelin13, and their corresponding negative controls were transfected into granulosa cell lines (KGN and SVOG) to monitor alterations in miR-16 expression, Apelin13, and PI3K/Akt signalling pathway-related proteins (p-Akt and Akt). MTT assay was used to detect cell viability, clone formation assay to detect cell proliferation, and flow cytometry to detect cell apoptosis rate. In addition, a luciferase assay was performed to test the targeting relationship between miR-16 and Apelin13. After miR-16 overexpression or Apelin13 knockdown was achieved in granulosa cells, granulosa cell proliferation was suppressed and cell apoptosis was enhanced. Additionally, Apelin13 is a potential target of miR-16. Functionally, overexpression of Apelin13 could partly reverse the effect of miR-16 overexpression on granulosa cell proliferation and apoptosis. Moreover, inhibits granulosa cell proliferation and enhances blocking the PI3K/Akt pathway by suppressing Apelin13. Our study revealed miR-16 regulates Apelin13 to mediate the PI3K/Akt signalling pathway and, thereby mediates PCOS progression.

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