TY - JOUR
T1 - Follicular Fluid-Derived Exosomal MicroRNA-18b-5p Regulates PTEN-Mediated PI3K/Akt/mTOR Signaling Pathway to Inhibit Polycystic Ovary Syndrome Development
AU - Zhou, Zhi
AU - Tu, Zhihua
AU - Zhang, Juan
AU - tan, Can
AU - Shen, Xiaoyong
AU - Wan, Bangbei
AU - Li, Yejuan
AU - Wang, Anguo
AU - Zhao, Liqiang
AU - Hu, Jiajia
AU - Ma, Ning
AU - Zhou, Jing
AU - Chen, Lin
AU - Song, Yanqin
AU - Lu, Weiying
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/4
Y1 - 2022/4
N2 - Small RNA sequences in follicular fluid (FF)-derived exosomes (extracellular vesicles contain proteins, DNA, and RNA) vitally function in the development of polycystic ovary syndrome (PCOS). It has been identified that microRNA (miR)-18b-5p is one of miRs that differ between control and PCOS women that passed the false discovery rate, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important modifier of biological functions of ovarian granulosa cells (GCs) in PCOS. However, whether miR-18b-5p could functionally mediate the progression of PCOS via PTEN was not clarified completely, which was the issue we wanted to solve in our research. FF-derived exosomes were isolated using an extraction kit. KGN cells were co-cultured with miR-18b-5p-modified exosomes or transfected with a PTEN-related vector. After treatment, cell proliferation and apoptosis were observed. A rat model of PCOS was established by letrozole and then injected with miR-18b-5p-modified exosomes. Then, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol (E2) levels in PCOS rats were measured. miR-18b-5p, PTEN, and phosphatidylinositol 3 kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related genes were tested. In PCOS patients, miR-18b-5p was downregulated, and PTEN was highly expressed in FF and GCs. PTEN knockdown increased KGN cell proliferation and limited apoptosis. FF-derived exosomes stimulated proliferation and suppressed apoptosis of KGN cells; decreased FSH, LH, and testosterone; and increased E2 in PCOS rats. Upregulating miR-18b-5p further enhanced the inhibitory effects of exosomes on suppressing the progression of PCOS. miR-18b-5p targeted PTEN and could activate PI3K/Akt/mTOR pathway. miR-18b-5p produced by FF-derived exosomes reduces PTEN expression and promotes the activation of the PI3K/Akt/mTOR signaling pathway to improve PCOS. Based on that, circulating miR-18b-5p levels can contribute to the progression of PCOS complications.
AB - Small RNA sequences in follicular fluid (FF)-derived exosomes (extracellular vesicles contain proteins, DNA, and RNA) vitally function in the development of polycystic ovary syndrome (PCOS). It has been identified that microRNA (miR)-18b-5p is one of miRs that differ between control and PCOS women that passed the false discovery rate, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important modifier of biological functions of ovarian granulosa cells (GCs) in PCOS. However, whether miR-18b-5p could functionally mediate the progression of PCOS via PTEN was not clarified completely, which was the issue we wanted to solve in our research. FF-derived exosomes were isolated using an extraction kit. KGN cells were co-cultured with miR-18b-5p-modified exosomes or transfected with a PTEN-related vector. After treatment, cell proliferation and apoptosis were observed. A rat model of PCOS was established by letrozole and then injected with miR-18b-5p-modified exosomes. Then, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol (E2) levels in PCOS rats were measured. miR-18b-5p, PTEN, and phosphatidylinositol 3 kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related genes were tested. In PCOS patients, miR-18b-5p was downregulated, and PTEN was highly expressed in FF and GCs. PTEN knockdown increased KGN cell proliferation and limited apoptosis. FF-derived exosomes stimulated proliferation and suppressed apoptosis of KGN cells; decreased FSH, LH, and testosterone; and increased E2 in PCOS rats. Upregulating miR-18b-5p further enhanced the inhibitory effects of exosomes on suppressing the progression of PCOS. miR-18b-5p targeted PTEN and could activate PI3K/Akt/mTOR pathway. miR-18b-5p produced by FF-derived exosomes reduces PTEN expression and promotes the activation of the PI3K/Akt/mTOR signaling pathway to improve PCOS. Based on that, circulating miR-18b-5p levels can contribute to the progression of PCOS complications.
KW - Follicular fluid-derived exosomes
KW - MicroRNA-18b-5p
KW - PI3K/Akt/mTOR pathway
KW - PTEN
KW - Polycystic ovary syndrome
UR - http://www.scopus.com/inward/record.url?scp=85123865420&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123865420&partnerID=8YFLogxK
U2 - 10.1007/s12035-021-02714-1
DO - 10.1007/s12035-021-02714-1
M3 - Article
C2 - 35092573
AN - SCOPUS:85123865420
SN - 0893-7648
VL - 59
SP - 2520
EP - 2531
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 4
ER -
