LncRNA DANCR counteracts premature ovarian insufficiency by regulating the senescence process of granulosa cells through stabilizing the interaction between p53 and hNRNPC
Tóm tắt
Premature ovarian insufficiency (POI) is one of the common women reproductive endocrine diseases which adversely impacts female fertility, but the etiology and pathogenesis still remain elusive. Recently increasing researches focus on the roles of lncRNA in POI. LncRNA DANCR was involved in cell differentiation and multiple cancers. It’s highly expressed in ovary while the role of DANCR in POI is still unknown. Here, we identify a new POI related lncRNA DANCR, which negatively contributes to ovarian granulosa cells aging and follicular atresia. DANCR is proved to be decreasingly expressed in POI patients’ granulosa cells. Additionally, Dancr knockout (Dancr−/−) mice were constructed and characterized with POI phenotypes and fertility decline, compared with Dancr+/+ mice. Further, in vitro experiments indicated that DANCR knockdown in granulosa cells led to cell aging and series of aging-related changes including proliferation inhibition, cell cycle G1 arrest and DNA damage. Mechanism research revealed DANCR binds with hNRNPC and p53, while DANCR knockdown attenuates the binding of hNRNPC and p53, thus enhancing protein level of p53 and promoting granulosa cells aging significantly. The newly identified lncRNA DANCR inhibits p53-dependent granulosa cells aging by regulating hNRNPC-p53 interaction, and eventually counteracting POI. This provides new insights into the pathogenesis of POI and provides a potential target for future diagnosis and treatment.
Tài liệu tham khảo
Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986;67:604–6.
Golezar S, Ramezani Tehrani F, Khazaei S, Ebadi A, Keshavarz Z. The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis. Climacteric. 2019;22:403–11.
Jiao X, Zhang H, Ke H, Zhang J, Cheng L, Liu Y, et al. Premature Ovarian Insufficiency: Phenotypic Characterization Within Different Etiologies. J Clin Endocrinol Metab. 2017;102:2281–90.
De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010;376:911–21.
Veitia RA. Primary ovarian insufficiency, meiosis and DNA repair. Biomed J. 2020;43:115–23.
Yu YS, Sui HS, Han ZB, Li W, Luo MJ, Tan JH. Apoptosis in granulosa cells during follicular atresia: relationship with steroids and insulin-like growth factors. Cell Res. 2004;14:341–6.
Yeung CK, Wang G, Yao Y, Liang J, Tenny Chung CY, Chuai M, et al. BRE modulates granulosa cell death to affect ovarian follicle development and atresia in the mouse. Cell Death Dis. 2017;8:e2697.
Wang J, Chu K, Wang Y, Li J, Fu J, Zeng YA, et al. Procr-expressing granulosa cells are highly proliferative and are important for follicle development. iScience. 2021;24:102065.
E F, Zhang H, Yin W, Wang C, Liu Y, Li Y, et al. CPEB3 deficiency in mice affect ovarian follicle development and causes premature ovarian insufficiency. Cell Death Dis. 2021;13:21.
Guo L, Liu X, Chen H, Wang W, Gu C, Li B. Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation. Aging (Albany NY). 2022;14:2335–47.
Jiang Z-x, Wang Y-n, Li Z-y, Dai Z-h, He Y, Chu K, et al. The m6A mRNA demethylase FTO in granulosa cells retards FOS-dependent ovarian aging. Cell Death Dis. 2021;12(8):744.
Tilly JL, Tilly KI, Perez GI. The genes of cell death and cellular susceptibility to apoptosis in the ovary: a hypothesis. Cell Death Differ. 1997;4:180–7.
Wang XY, Qin YY. Long non-coding RNAs in biology and female reproductive disorders. Front Biosci (Landmark Ed). 2019;24:750–64.
Pankiewicz K, Laudanski P, Issat T. The Role of Noncoding RNA in the Pathophysiology and Treatment of Premature Ovarian Insufficiency. Int J Mol Sci. 2021;22:9336.
Yao G, He J, Kong Y, Zhai J, Xu Y, Yang G, et al. Transcriptional profiling of long noncoding RNAs and their target transcripts in ovarian cortical tissues from women with normal menstrual cycles and primary ovarian insufficiency. Mol Reprod Dev. 2019;86:847–61.
Wang X, Zhang X, Dang Y, Li D, Lu G, Chan WY, et al. Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1. Nucleic Acids Res. 2020;48:4480–91.
Li D, Wang X, Dang Y, Zhang X, Zhao S, Lu G, et al. lncRNA GCAT1 is involved in premature ovarian insufficiency by regulating p27 translation in GCs via competitive binding to PTBP1. Mol Ther Nucleic Acids. 2021;23:132–41.
Li D, Wang X, Li G, Dang Y, Zhao S, Qin Y. LncRNA ZNF674-AS1 regulates granulosa cell glycolysis and proliferation by interacting with ALDOA. Cell Death Discov. 2021;7:107.
Li D, Xu W, Wang X, Dang Y, Xu L, Lu G, et al. lncRNA DDGC participates in premature ovarian insufficiency through regulating RAD51 and WT1. Mol Ther Nucleic Acids. 2021;26:1092–106.
Zheng C, Liu S, Qin Z, Zhang X, Song Y. LncRNA DLEU1 is overexpressed in premature ovarian failure and sponges miR-146b-5p to increase granulosa cell apoptosis. J Ovarian Res. 2021;14:151.
Zhang L, Mao B, Zhao X, Yuan Y, Wang W, Lin S. Translation regulatory long non-coding RNA 1 (TRERNA1) sponges microRNA-23a to suppress granulosa cell apoptosis in premature ovarian failure. Bioengineered. 2022;13:2173–80.
Kretz M, Webster DE, Flockhart RJ, Lee CS, Zehnder A, Lopez-Pajares V, et al. Suppression of progenitor differentiation requires the long noncoding RNA ANCR. Genes Dev. 2012;26:338–43.
Zhang Z, Shu L, Hu M, Zhou X, Yang F, Zhou XH. Emerging role of lncRNA DANCR in progenitor cells: beyond cancer. Eur Rev Med Pharmacol Sci. 2021;25:1399–409.
Jin SJ, Jin MZ, Xia BR, Jin WL. Long Non-coding RNA DANCR as an Emerging Therapeutic Target in Human Cancers. Front Oncol. 2019;9:1225.
Wang M, Gu J, Zhang X, Yang J, Zhang X, Fang X. Long Non-coding RNA DANCR in Cancer: Roles, Mechanisms, and Implications. Front Cell Dev Biol. 2021;9:753706.
Fagerberg L, Hallstrom BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2014;13:397–406.
Xu X, Chen X, Zhang X, Liu Y, Wang Z, Wang P, et al. Impaired telomere length and telomerase activity in peripheral blood leukocytes and granulosa cells in patients with biochemical primary ovarian insufficiency. Hum Reprod. 2017;32:201–7.
Sheekey E, Narita M. p53 in senescence - it's a marathon not a sprint. FEBS J. 2021. https://doi.org/10.1111/febs.16325.
Rufini A, Tucci P, Celardo I, Melino G. Senescence and aging: the critical roles of p53. Oncogene. 2013;32:5129–43.
Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005;120:513–22.
Siprashvili Z, Webster DE, Kretz M, Johnston D, Rinn JL, Chang HY, et al. Identification of proteins binding coding and non-coding human RNAs using protein microarrays. BMC Genomics. 2012;13:633.
Barry G, Briggs JA, Vanichkina DP, Poth EM, Beveridge NJ, Ratnu VS, et al. The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Mol Psychiatry. 2014;19:486–94.
Shen Y, Liu S, Fan J, Jin Y, Tian B, Zheng X, et al. Nuclear retention of the lncRNA SNHG1 by doxorubicin attenuates hnRNPC-p53 protein interactions. EMBO Rep. 2017;18:536–48.
Zarnack K, König J, Tajnik M, Martincorena I, Eustermann S, Stévant I, et al. Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements. Cell. 2013;152:453–66.
Yuan SX, Wang J, Yang F, Tao QF, Zhang J, Wang LL, et al. Long noncoding RNA DANCR increases stemness features of hepatocellular carcinoma by derepression of CTNNB1. Hepatology. 2016;63:499–511.
Lin X, Yang F, Qi X, Li Q, Wang D, Yi T, et al. LncRNA DANCR promotes tumor growth and angiogenesis in ovarian cancer through direct targeting of miR-145. Mol Carcinog. 2019;58:2286–96.
Thin KZ, Liu X, Feng X, Raveendran S, Tu JC. LncRNA-DANCR: A valuable cancer related long non-coding RNA for human cancers. Pathol Res Pract. 2018;214:801–5.
Hatzirodos N, Hummitzsch K, Irving-Rodgers HF, Harland ML, Morris SE, Rodgers RJ. Transcriptome profiling of granulosa cells from bovine ovarian follicles during atresia. BMC Genomics. 2014;15:40.
Regan SLP, Knight PG, Yovich JL, Leung Y, Arfuso F, Dharmarajan A. Granulosa Cell Apoptosis in the Ovarian Follicle-A Changing View. Front Endocrinol (Lausanne). 2018;9:61.
Zhou J, Peng X, Mei S. Autophagy in Ovarian Follicular Development and Atresia. Int J Biol Sci. 2019;15:726–37.
Chaudhary GR, Yadav PK, Yadav AK, Tiwari M, Gupta A, Sharma A, et al. Necroptosis in stressed ovary. J Biomed Sci. 2019;26:11.
Ferrè F, Colantoni A, Helmer-Citterich M. Revealing protein-lncRNA interaction. Brief Bioinform. 2016;17:106–16.
Kopp F, Mendell JT. Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell. 2018;172:393–407.
Choi YD, Grabowski PJ, Sharp PA, Dreyfuss G. Heterogeneous nuclear ribonucleoproteins: role in RNA splicing. Science. 1986;231:1534–9.
Christian KJ, Lang MA, Raffalli-Mathieu F. Interaction of heterogeneous nuclear ribonucleoprotein C1/C2 with a novel cis-regulatory element within p53 mRNA as a response to cytostatic drug treatment. Mol Pharmacol. 2008;73:1558–67.
Webber L, Davies M, Anderson R, Bartlett J, Braat D, Cartwright B, et al. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31:926–37.
Dong JP, Dai ZH, Jiang ZX, He Y, Wang L, Liao QY, et al. CD24: a marker of granulosa cell subpopulation and a mediator of ovulation. Cell Death Dis. 2019;10:791.
Gan X, Ding D, Wang M, Yang Y, Sun D, Li W, et al. DANCR deletion retards the initiation and progression of hepatocellular carcinoma based on gene knockout and patient-derived xenograft in situ hepatoma mice model. Cancer Lett. 2022;550: 215930.
Cora MC, Kooistra L, Travlos G. Vaginal Cytology of the Laboratory Rat and Mouse: Review and Criteria for the Staging of the Estrous Cycle Using Stained Vaginal Smears. Toxicol Pathol. 2015;43:776–93.