MicroRNA-379-5p is associated with biochemical premature ovarian insufficiency through PARP1 and XRCC6

Cell Death and Disease - Tập 9 Số 2
Yujie Dang1, Xiaoyan Wang2, Yajing Hao3, Xinyue Zhang2, Shidou Zhao2, Jinlong Ma2, Yingying Qin2, Zi‐Jiang Chen2
1Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001, China
2Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China
3Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China

Tóm tắt

AbstractPremature ovarian insufficiency (POI) imposes great challenges on women’s fertility and lifelong health. POI is highly heterogeneous and encompasses occult, biochemical, and overt stages. MicroRNAs (miRNAs) are negative regulators of gene expression, whose roles in physiology and diseases like cancers and neurological disorders have been recognized, but little is known about the miRNAs profile and functional relevance in biochemical POI (bPOI). In this study, the expression of miRNAs and mRNAs in granulosa cells (GCs) of bPOI women was determined by two microarrays, respectively. MiR-379-5p, PARP1, and XRCC6 were differentially expressed in GCs of bPOI as revealed by microarrays. Subsequently, functional studies demonstrated that miR-379-5p overexpression inhibited granulosa cell proliferation and attenuated DNA repair efficiency. Furthermore, both PARP1 and XRCC6 showed lower levels in GCs from patients with bPOI and were identified as executives of miR-379-5p. Therefore, our data first uncovered potentially pathogenic miR-379-5p and two novel targets PARP1 and XRCC6 in bPOI, which corroborated the significance of DNA repair for POI, and brought up an epigenetic explanation for the disease.

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Tài liệu tham khảo

Nelson, L. M. Clinical practice. Primary ovarian insufficiency. N. Engl. J. Med. 360, 606–614 (2009).

European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI, Webber, L. et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum. Reprod. 31, 926–937 (2016).

Wu, X. et al. Impact of premature ovarian failure on mortality and morbidity among Chinese women. PLoS ONE 9, e89597 (2014).

Welt, C. K. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin. Endocrinol. 68, 499–509 (2008).

Knauff, E. A. et al. Anti-Mullerian hormone, inhibin B, and antral follicle count in young women with ovarian failure. J. Clin. Endocrinol. Metab. 94, 786–792 (2009).

De Vos, M., Devroey, P. & Fauser, B. C. Primary ovarian insufficiency. Lancet 376, 911–921 (2010).

Jorgez, C. J., Klysik, M., Jamin, S. P., Behringer, R. R. & Matzuk, M. M. Granulosa cell-specific inactivation of follistatin causes female fertility defects. Mol. Endocrinol. 18, 953–967 (2004).

Edson, M. A., Nagaraja, A. K. & Matzuk, M. M. The mammalian ovary from genesis to revelation. Endocr. Rev. 30, 624–712 (2009).

Matsuda, F., Inoue, N., Manabe, N. & Ohkura, S. Follicular growth and atresia in mammalian ovaries: regulation by survival and death of granulosa cells. J. Reprod. Dev. 58, 44–50 (2012).

Dong, J. et al. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383, 531–535 (1996).

Lechowska, A. et al. Premature ovarian failure in nobox-deficient mice is caused by defects in somatic cell invasion and germ cell cyst breakdown. J. Assist. Reprod. Genet. 28, 583–589 (2011).

Sirotkin, A. V., Ovcharenko, D., Grossmann, R., Lauková, M. & Mlyncek, M. Identification of microRNAs controlling human ovarian cell steroidogenesis via a genome-scale screen. J. Cell Physiol. 219, 415–420 (2009).

Imbar, T. & Eisenberg, I. Regulatory role of microRNAs in ovarian function. Fertil. Steril. 101, 1524–1530 (2014).

Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004).

Esteller, M. Non-coding RNAs in human disease. Nat. Rev. Genet. 12, 861–874 (2011).

Rah, H. et al. Association of miR-146aC>G, miR-196a2T>C, and miR-499A>G polymorphisms with risk of premature ovarian failure in Korean women. Reprod. Sci. 20, 60–68 (2013).

Pan, H. et al. The miR-449b polymorphism, rs10061133 A>G, is associated with premature ovarian insufficiency. Menopause 23, 1009–1011 (2016).

Yang, X. et al. Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis. Reproduction 144, 235–244 (2012).

Zhang, Q. et al. MicroRNA-181a suppresses mouse granulosa cell proliferation by targeting activin receptor IIA. PLoS ONE 8, e59667 (2013).

Dang, Y. et al. MicroRNA-22-3p is down-regulated in the plasma of Han Chinese patients with premature ovarian failure. Fertil. Steril. 103, 802–807.e1 (2015).

Chen, X., Xie, M., Liu, D. & Shi, K. Down regulation of microRNA-146a inhibits ovarian granulosa cell apoptosis by simultaneously targeting interleukin-1 receptor-associated kinase and tumor necrosis factor receptor-associated factor 6. Mol. Med. Rep. 12, 5155–5162 (2015).

da Rocha, S. T., Edwards, C. A., Ito, M., Ogata, T. & Ferguson-Smith, A. C. Genomic imprinting at the mammalian Dlk1-Dio3 domain. Trends Genet. 24, 306–316 (2008).

Stadtfeld, M. et al. Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature 465, 175–181 (2010).

Gardiner, E. et al. Imprinted DLK1-DIO3 region of 14q32 defines a schizophrenia-associated miRNA signature in peripheral blood mononuclear cells. Mol. Psychiatry 17, 827–840 (2012).

Labialle, S. et al. The miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 domain controls neonatal metabolic adaptation. EMBO J. 33, 2216–2230 (2014).

Khan, S. et al. MiR-379 regulates cyclin B1 expression and is decreased in breast cancer. PLoS ONE 8, e68753 (2013).

Gururajan, M. et al. miR-154* and miR-379 in the DLK1-DIO3 microRNA mega-cluster regulate epithelial to mesenchymal transitionand bone metastasis of prostate cancer. Clin. Cancer Res. 20, 6559–6569 (2014).

Chen, J. S. et al. MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma. Cancer Lett. 375, 73–83 (2016).

AlAsiri, S. et al. Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability. J. Clin. Invest. 125, 258–262 (2015).

Dou, X. et al. Minichromosome maintenance complex component 8 mutations cause primary ovarian insufficiency. Fertil. Steril. 106, 1485–1489.e2 (2016).

Wood-Trageser, M. A. et al. MCM9 mutations are associated with ovarian failure, short stature, and chromosomal instability. Am. J. Hum. Genet. 95, 754–762 (2014).

Desai, S. et al. MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency. J. Clin. Endocrinol. Metab. 102, 576–582 (2017).

Qin, Y. et al. CSB-PGBD3 mutations cause premature ovarian failure. PLoS Genet. 11, e1005419 (2015).

Guo, T. et al. Mutations in MSH5 in primary ovarian insufficiency. Hum. Mol. Genet. 26, 1452–1457 (2017).

He, C. et al. Genome-wide association studies identify loci associated with age at menarche and age at natural menopause. Nat. Genet. 41, 724–728 (2009).

He, C. et al. A large-scale candidate gene association study of age at menarche and age at natural menopause. Hum. Genet. 128, 515–527 (2010).

Stolk, L. et al. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nat. Genet. 44, 260–268 (2012).

Day, F. R. et al. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nat. Genet. 47, 1294–1303 (2015).

Rouleau, M., Patel, A., Hendzel, M. J., Kaufmann, S. H. & Poirier, G. G. PARP inhibition: PARP1 and beyond. Nat. Rev. Cancer 10, 293–301 (2010).

Celli, G. B., Denchi, E. L. & de Lange, T. Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination. Nat. Cell Biol. 8, 885–890 (2006).

Jiang, L. et al. MicroRNA-93 promotes ovarian granulosa cells proliferation through targeting CDKN1A in polycystic ovarian syndrome. J. Clin. Endocrinol. Metab. 100, E729–E738 (2015).

Gao, F. et al. Wt1 functions in ovarian follicle development by regulating granulosa cell differentiation. Hum. Mol. Genet. 23, 333–341 (2014).

Titus, S. et al. Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans. Sci. Transl. Med. 5, 172ra21 (2013).

Oktay, K., Turan, V., Titus, S., Stobezki, R. & Liu, L. BRCA mutations, DNA repair deficiency, and ovarian aging. Biol. Reprod. 93, 67 (2015).

Zhang, D. et al. Increased DNA damage and repair deficiency in granulosa cells are associated with ovarian aging in rhesus monkey. J. Assist. Reprod. Genet. 32, 1069–1078 (2015).

Bürkle, A., Beneke, S. & Muiras, M. L. Poly(ADP-ribosyl)ation and aging. Exp. Gerontol. 39, 1599–1601 (2004).

Bai, P. & Cantó, C. The role of PARP-1 and PARP-2 enzymes in metabolic regulation and disease. Cell Metab. 16, 290–295 (2012).

Shimizu, I., Yoshida, Y., Suda, M. & Minamino, T. DNA damage response and metabolic disease. Cell Metab. 20, 967–977 (2014).

Downs, J. A. & Jackson, S. P. A means to a DNA end: the many roles of Ku. Nat. Rev. Mol. Cell Biol. 5, 367–378 (2004).

Ménissier de Murcia, J. et al. Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse. EMBO J. 22, 2255–2263 (2003).

Piskunova T. S. et al. Deficiency in poly (ADP-ribose) polymerase-1 (PARP-1) accelerates aging and spontaneous carcinogenesis in mice. Curr. Gerontol. Geriatr. Res. 2008, 754190 (2008).

Gu, Y. et al. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity 7, 653–665 (1997).

Li, H., Vogel, H., Holcomb, V. B., Gu, Y. & Hasty, P. Deletion of Ku70, Ku80, or both causes early aging without substantially increased cancer. Mol. Cell Biol. 27, 8205–8214 (2007).

Ma, T. et al. Microarray analysis of differentially expressed microRNAs in non-regressed and regressed bovine corpus luteum tissue; microRNA-378 may suppress luteal cell apoptosis by targeting the interferon gamma receptor 1 gene. J. Appl. Genet. 52, 481–486 (2011).

Tesfaye, D. et al. Identification and expression profiling of microRNAs during bovine oocyte maturation using heterologous approach. Mol. Reprod. Dev. 76, 665–677 (2009).

da Silveira, J. C., Veeramachaneni, D. N., Winger, Q. A., Carnevale, E. M. & Bouma, G. J. Cell-secreted vesicles in equine ovarian follicular fluid contain miRNAs and proteins: a possible new form of cell communication within the ovarian follicle. Biol. Reprod. 86, 71 (2012).

Jiao X. et al. Premature ovarian insufficiency: phenotypic characterization within different etiologies. J. Clin. Endocrinol. Metab. https://doi.org/10.1210/jc.2016-3960 (2017)..

Xu, X. et al. Impaired telomere length and telomerase activity in peripheral blood leukocytes and granulosa cells in patients with biochemical primary ovarian insufficiency. Hum. Reprod. 32, 201–207 (2017).

Nishi, Y. et al. Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor. Endocrinology 142, 437–445 (2001).

Patel, A. G., Sarkaria, J. N. & Kaufmann, S. H. Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proc. Natl Acad. Sci. USA 108, 3406–3411 (2011).

Ström, C. E., Johansson, F., Uhlén, M., Szigyarto, C. A., Erixon, K., Helleday, T. Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediate. Nucleic Acids Res. 39, 3166–3175 (2011).