MicroRNA-200b and MicroRNA-200c Are Up-regulated in PCOS Granulosa Cell and Inhibit KGN Cell Proliferation Via Targeting PTEN

Overview

Journal Reprod Biol Endocrinol

Publisher Biomed Central

Specialties Endocrinology
Reproductive Medicine

Date 2019 Aug 19

PMID 31421682

Citations 25

Authors

Tingting He

Yifei Sun

Yingchun Zhang

Shigang Zhao

Yanjun Zheng

Guimin Hao

Yuhua Shi

Affiliations

Soon will be listed here.

Abstract

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders characterized by hyperandrogenism, polycystic ovaries and ovulatory dysfunction. Several studies have reported that the aberrant expression of miRNAs contributes a lot to disordered folliculogenesis in PCOS, though the role and underlying mechanism of microRNA-200b (miR-200b) and microRNA-200c (miR-200c) in the development of PCOS remain unclear.

Methods: The expression of miR-200b in granulosa cells (GCs) derived from 90 PCOS patients and 70 controls was analyzed by using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Granulosa-like tumor cell line (KGN) was cultured for cell counting kit-8 (CCK-8) assays after over-expression of miR-200b, miR-200c or knockdown phosphatase and tensin homolog (PTEN). TargetScan was used to identify the potential targets of miR-200b and miR-200c, which was further verified by qRT-PCR, western blot and luciferase assays.

Results: Significantly increased expression of miR-200b was observed in PCOS patients compared with the controls. Moreover, over-expression of miR-200b and miR-200c inhibited the proliferation of KGN cells. In addition, our results verified that miR-200b and miR-200c directly targeted PTEN, knockdown of which suppressed KGN cells proliferation.

Conclusion: Our findings demonstrate that miR-200b and miR-200c suppress the proliferation of KGN cells by targeting PTEN, and this might provide new evidence for abnormal proliferation of GCs in PCOS.

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References

Nishi Y, Yanase T, Mu Y, Oba K, Ichino I, Saito M . Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor. Endocrinology. 2001; 142(1):437-45. DOI: 10.1210/endo.142.1.7862. View

Eppig J . Oocyte control of ovarian follicular development and function in mammals. Reproduction. 2001; 122(6):829-38. DOI: 10.1530/rep.0.1220829. View

Webber L, Stubbs S, Stark J, Trew G, Margara R, Hardy K . Formation and early development of follicles in the polycystic ovary. Lancet. 2003; 362(9389):1017-21. DOI: 10.1016/s0140-6736(03)14410-8. View

. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81(1):19-25. DOI: 10.1016/j.fertnstert.2003.10.004. View

Maciel G, Baracat E, Benda J, Markham S, Hensinger K, Chang R . Stockpiling of transitional and classic primary follicles in ovaries of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004; 89(11):5321-7. DOI: 10.1210/jc.2004-0643. View

Norman R, Dewailly D, Legro R, Hickey T . Polycystic ovary syndrome. Lancet. 2007; 370(9588):685-97. DOI: 10.1016/S0140-6736(07)61345-2. View

Carletti M, Christenson L . MicroRNA in the ovary and female reproductive tract. J Anim Sci. 2008; 87(14 Suppl):E29-38. PMC: 3118666. DOI: 10.2527/jas.2008-1331. View

Sirotkin A, Ovcharenko D, Grossmann R, Laukova M, Mlyncek M . Identification of microRNAs controlling human ovarian cell steroidogenesis via a genome-scale screen. J Cell Physiol. 2009; 219(2):415-20. DOI: 10.1002/jcp.21689. View

Goto M, Iwase A, Harata T, Takigawa S, Suzuki K, Manabe S . IGF1-induced AKT phosphorylation and cell proliferation are suppressed with the increase in PTEN during luteinization in human granulosa cells. Reproduction. 2009; 137(5):835-42. DOI: 10.1530/REP-08-0315. View

10.

Iwase A, Goto M, Harata T, Takigawa S, Nakahara T, Suzuki K . Insulin attenuates the insulin-like growth factor-I (IGF-I)-Akt pathway, not IGF-I-extracellularly regulated kinase pathway, in luteinized granulosa cells with an increase in PTEN. J Clin Endocrinol Metab. 2009; 94(6):2184-91. DOI: 10.1210/jc.2008-1948. View

11.

Sirotkin A, Laukova M, Ovcharenko D, Brenaut P, Mlyncek M . Identification of microRNAs controlling human ovarian cell proliferation and apoptosis. J Cell Physiol. 2009; 223(1):49-56. DOI: 10.1002/jcp.21999. View

12.

Goodarzi M, Dumesic D, Chazenbalk G, Azziz R . Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011; 7(4):219-31. DOI: 10.1038/nrendo.2010.217. View

13.

Chang R, Cook-Andersen H . Disordered follicle development. Mol Cell Endocrinol. 2012; 373(1-2):51-60. PMC: 3727408. DOI: 10.1016/j.mce.2012.07.011. View

14.

Shi Y, Zhao H, Shi Y, Cao Y, Yang D, Li Z . Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nat Genet. 2012; 44(9):1020-5. DOI: 10.1038/ng.2384. View

15.

Yates L, Norbury C, Gilbert R . The long and short of microRNA. Cell. 2013; 153(3):516-9. DOI: 10.1016/j.cell.2013.04.003. View

16.

Dou L, Zhao T, Wang L, Huang X, Jiao J, Gao D . miR-200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes. J Biol Chem. 2013; 288(31):22596-606. PMC: 3829346. DOI: 10.1074/jbc.M112.423145. View

17.

Zhang W, Wei D, Sun X, Li J, Yu X, Shi Y . Family-based analysis of adiponectin gene polymorphisms in Chinese Han polycystic ovary syndrome. Fertil Steril. 2014; 101(5):1419-23. DOI: 10.1016/j.fertnstert.2014.01.035. View

18.

Nandi A, Chen Z, Patel R, Poretsky L . Polycystic ovary syndrome. Endocrinol Metab Clin North Am. 2014; 43(1):123-47. DOI: 10.1016/j.ecl.2013.10.003. View

19.

Acunzo M, Romano G, Wernicke D, Croce C . MicroRNA and cancer--a brief overview. Adv Biol Regul. 2014; 57:1-9. DOI: 10.1016/j.jbior.2014.09.013. View

20.

Xu B, Zhang Y, Tong X, Liu Y . Characterization of microRNA profile in human cumulus granulosa cells: Identification of microRNAs that regulate Notch signaling and are associated with PCOS. Mol Cell Endocrinol. 2015; 404:26-36. DOI: 10.1016/j.mce.2015.01.030. View