The Role of LncRNA as CeRNA in Polycystic Ovary Syndrome

doi:10.12280/gjszjk.20230416

Abstract

Abstract:

Polycystic ovary syndrome (PCOS) is a common female reproductive endocrine disorder that is related with various factors including epigenetic and environment. Long non-coding RNA (lncRNA), with more than 200 nucleotides, are a kind of RNA molecules that do not code proteins. LncRNA can affect the expression of gene through epigenetic modification, transcriptional and post-transcriptional regulation. As a kind of competing endogenous RNA (ceRNA), lncRNA can affect the expression of target gene by competitively binding microRNA (miRNA). As a new regulatory mechanism, it can play an important role in many biological processes such as cell proliferation and differentiation, inflammatory response and immune response, which is closely related to many diseases. The ceRNA hypothesis also provides a further understanding of the mechanism of PCOS. Recently, the studies of lncRNA in PCOS significantly increased. The lncRNA differentially expressed in PCOS can involve as ceRNA in ovarian granulosa cell proliferation, oocyte maturation as well as hormone synthesis, and play an potential role in the development of PCOS. In this review, we summarize the roles of lncRNA as ceRNA in the occurrence and development of PCOS.

Key words: Polycystic ovary syndrome, RNA, long noncoding, Competing endogenous RNA, Gene expression, Ovary

DAI He-qi, MAO Fei, FENG Rui-zhi, QIAN Yun. The Role of LncRNA as CeRNA in Polycystic Ovary Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(2): 144-149.

References 46

[1]	Wang QY, Song Y, Huang W, et al. Comparison of Drospirenone- with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial[J]. Chin Med J(Engl), 2016, 129(8):883-890. doi: 10.4103/0366-6999.179783.
[2]	De Leo V, Musacchio MC, Cappelli V, et al. Genetic, hormonal and metabolic aspects of PCOS: an update[J]. Reprod Biol Endocrinol, 2016, 14(1):38. doi: 10.1186/s12958-016-0173-x.
[3]	Harada M. Pathophysiology of polycystic ovary syndrome revisited: Current understanding and perspectives regarding future research[J]. Reprod Med Biol, 2022, 21(1):e12487. doi: 10.1002/rmb2.12487.
[4]	Yin W, Falconer H, Yin L, et al. Association Between Polycystic Ovary Syndrome and Cancer Risk[J]. JAMA Oncol, 2019, 5(1):106-107. doi: 10.1001/jamaoncol.2018.5188. pmid: 30489606
[5]	Banaszewska B, Pawelczyk L, Spaczynski R. Current and future aspects of several adjunctive treatment strategies in polycystic ovary syndrome[J]. Reprod Biol, 2019, 19(4):309-315. doi: 10.1016/j.repbio.2019.09.006. pmid: 31606349
[6]	Hashemi M, Moosavi MS, Abed HM, et al. Long non-coding RNA (lncRNA) H19 in human cancer: From proliferation and metastasis to therapy[J]. Pharmacol Res, 2022,184:106418. doi: 10.1016/j.phrs.2022.106418.
[7]	Mattick JS, Amaral PP, Carninci P, et al. Long non-coding RNAs: definitions, functions, challenges and recommendations[J]. Nat Rev Mol Cell Biol, 2023, 24(6):430-447. doi: 10.1038/s41580-022-00566-8.
[8]	Palazzo AF, Koonin EV. Functional Long Non-coding RNAs Evolve from Junk Transcripts[J]. Cell, 2020, 183(5):1151-1161. doi: 10.1016/j.cell.2020.09.047. pmid: 33068526
[9]	Dhanoa JK, Sethi RS, Verma R, et al. Long non-coding RNA: its evolutionary relics and biological implications in mammals: a review[J]. J Anim Sci Technol, 2018,60:25. doi: 10.1186/s40781-018-0183-7.
[10]	Statello L, Guo CJ, Chen LL, et al. Gene regulation by long non-coding RNAs and its biological functions[J]. Nat Rev Mol Cell Biol, 2021, 22(2):96-118. doi: 10.1038/s41580-020-00315-9.
[11]	Abbasifard M, Kamiab Z, Bagheri-Hosseinabadi Z, et al. The role and function of long non-coding RNAs in osteoarthritis[J]. Exp Mol Pathol, 2020,114:104407. doi: 10.1016/j.yexmp.2020.104407.
[12]	Salmena L, Poliseno L, Tay Y, et al. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?[J]. Cell, 2011, 146(3):353-358. doi: 10.1016/j.cell.2011.07.014. pmid: 21802130
[13]	Mullany LE, Herrick JS, Wolff RK, et al. Impact of polymorphisms in microRNA biogenesis genes on colon cancer risk and microRNA expression levels: a population-based, case-control study[J]. BMC Med Genomics, 2016, 9(1):21. doi: 10.1186/s12920-016-0181-x. pmid: 27107574
[14]	Zhao H, He Y, Li H, et al. The opposite role of alternatively spliced isoforms of LINC00477 in gastric cancer[J]. Cancer Manag Res, 2019, 11:4569-4576. doi: 10.2147/CMAR.S202430. pmid: 31191018
[15]	Gao H, Jiang J, Shi Y, et al. The LINC00477/miR-128 axis promotes the progression of polycystic ovary syndrome by regulating ovarian granulosa cell proliferation and apoptosis[J]. Reprod Biol Endocrinol, 2021, 19(1):29. doi: 10.1186/s12958-021-00718-z.
[16]	Das M, Djahanbakhch O, Hacihanefioglu B, et al. Granulosa cell survival and proliferation are altered in polycystic ovary syndrome[J]. J Clin Endocrinol Metab, 2008, 93(3):881-887. doi: 10.1210/jc.2007-1650.
[17]	Jiang B, Xue M, Xu D, et al. Down-regulated lncRNA HOTAIR alleviates polycystic ovaries syndrome in rats by reducing expression of insulin-like growth factor 1 via microRNA-130a[J]. J Cell Mol Med, 2020, 24(1):451-464. doi: 10.1111/jcmm.14753. pmid: 31733099
[18]	Hasegawa T, Kamada Y, Hosoya T, et al. A regulatory role of androgen in ovarian steroidogenesis by rat granulosa cells[J]. J Steroid Biochem Mol Biol, 2017, 172:160-165. doi: 10.1016/j.jsbmb.2017.07.002.
[19]	Mani AM, Fenwick MA, Cheng Z, et al. IGF1 induces up-regulation of steroidogenic and apoptotic regulatory genes via activation of phosphatidylinositol-dependent kinase/AKT in bovine granulosa cells[J]. Reproduction, 2010, 139(1):139-151. doi: 10.1530/REP-09-0050. pmid: 19819918
[20]	Batista JG, Soares JM Jr, Maganhin CC, et al. Assessing the benefits of rosiglitazone in women with polycystic ovary syndrome through its effects on insulin-like growth factor 1, insulin-like growth factor-binding protein-3 and insulin resistance: a pilot study[J]. Clinics(Sao Paulo), 2012, 67(3):283-287. doi: 10.6061/clinics/2012(03)14.
[21]	Wawrzik M, Spiess AN, Herrmann R, et al. Expression of SNURF-SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis[J]. Eur J Hum Genet, 2009, 17(11):1463-1470. doi: 10.1038/ejhg.2009.83. pmid: 19471314
[22]	Huang X, Pan J, Wu B, et al. Construction and analysis of a lncRNA (PWRN2)-mediated ceRNA network reveal its potential roles in oocyte nuclear maturation of patients with PCOS[J]. Reprod Biol Endocrinol, 2018, 16(1):73. doi: 10.1186/s12958-018-0392-4.
[23]	Batrakou DG, de Las Heras JI, Czapiewski R, et al. TMEM120A and B: Nuclear Envelope Transmembrane Proteins Important for Adipocyte Differentiation[J]. PLoS One, 2015, 10(5):e0127712. doi: 10.1371/journal.pone.0127712.
[24]	Machtinger R, Combelles CM, Missmer SA, et al. The association between severe obesity and characteristics of failed fertilized oocytes[J]. Hum Reprod, 2012, 27(11):3198-3207. doi: 10.1093/humrep/des308.
[25]	Zhang Y, Mi L, Xuan Y, et al. LncRNA HOTAIRM1 inhibits the progression of hepatocellular carcinoma by inhibiting the Wnt signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2018, 22(15):4861-4868. doi: 10.26355/eurrev_201808_15622.
[26]	Li X, Pang L, Yang Z, et al. LncRNA HOTAIRM1/HOXA1 Axis Promotes Cell Proliferation, Migration And Invasion In Endometrial Cancer[J]. Onco Targets Ther, 2019, 12:10997-11015. doi: 10.2147/OTT.S222334.
[27]	Kim CY, Oh JH, Lee JY, et al. The LncRNA HOTAIRM1 Promotes Tamoxifen Resistance by Mediating HOXA1 Expression in ER+ Breast Cancer Cells[J]. J Cancer, 2020, 11(12):3416-3423. doi: 10.7150/jca.38728. pmid: 32284737
[28]	Guo H, Li T, Sun X. LncRNA HOTAIRM1, miR-433-5p and PIK3CD function as a ceRNA network to exacerbate the development of PCOS[J]. J Ovarian Res, 2021, 14(1):19. doi: 10.1186/s13048-020-00742-4. pmid: 33485372
[29]	Zhao H, Ding F, Zheng G. LncRNA TMPO-AS1 promotes LCN2 transcriptional activity and exerts oncogenic functions in ovarian cancer[J]. FASEB J, 2020, 34(9):11382-11394. doi: 10.1096/fj.201902683R.
[30]	Mitobe Y, Ikeda K, Suzuki T, et al. ESR1-Stabilizing Long Noncoding RNA TMPO-AS1 Promotes Hormone-Refractory Breast Cancer Progression[J]. Mol Cell Biol, 2019, 39(23):e00261-19. doi: 10.1128/MCB.00261-19.
[31]	Hou F, Li J, Peng J, et al. LncRNA TMPO-AS1 suppresses the maturation of miR-335-5p to participate in polycystic ovary syndrome[J]. J Ovarian Res, 2021, 14(1):99. doi: 10.1186/s13048-021-00848-3. pmid: 34330309
[32]	Yao L, Li M, Hu J, et al. MiRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS[J]. Reproduction, 2018, 156(5):439-449. doi: 10.1530/REP-18-0229. pmid: 30328340
[33]	ElMonier AA, El-Boghdady NA, Fahim SA, et al. LncRNA NEAT1 and MALAT1 are involved in polycystic ovary syndrome pathogenesis by functioning as competing endogenous RNAs to control the expression of PCOS-related target genes[J]. Noncoding RNA Res, 2023, 8(2):263-271. doi: 10.1016/j.ncrna.2023.02.008. pmid: 36935861
[34]	Wu L, Tu Z, Bao Y, et al. Long noncoding RNA NEAT1 decreases polycystic ovary syndrome progression via the modulation of the microRNA-324-3p and BRD3 axis[J]. Cell Biol Int, 2022, 46(12):2075-2084. doi: 10.1002/cbin.11893.
[35]	Jiang YC, Ma JX. The role of MiR-324-3p in polycystic ovary syndrome (PCOS) via targeting WNT2B[J]. Eur Rev Med Pharmacol Sci, 2018, 22(11):3286-3293. doi: 10.26355/eurrev_201806_15147.
[36]	Zheng Y, Lv P, Wang S, et al. LncRNA PLAC2 upregulates p53 to induce hepatocellular carcinoma cell apoptosis[J]. Gene, 2019, 712:143944. doi: 10.1016/j.gene.2019.143944.
[37]	Li G, Wang Y, Wang J, et al. Long non-coding RNA placenta-specific protein 2 regulates micorRNA-19a/tumor necrosis factor α to participate in polycystic ovary syndrome[J]. Bioengineered, 2022, 13(1):856-862. doi: 10.1080/21655979.2021.2013722.
[38]	Mohammadi S, Kayedpoor P, Karimzadeh-Bardei L, et al. The Effect of Curcumin on TNF-α, IL-6 and CRP Expression in a Model of Polycystic Ovary Syndrome as an Inflammation State[J]. J Reprod Infertil, 2017, 18(4):352-360. pmid: 29201665
[39]	Zhu HL, Chen YQ, Zhang ZF. Downregulation of lncRNA ZFAS1 and upregulation of microRNA-129 repress endocrine disturbance, increase proliferation and inhibit apoptosis of ovarian granulosa cells in polycystic ovarian syndrome by downregulating HMGB1[J]. Genomics, 2020, 112(5):3597-3608. doi: 10.1016/j.ygeno.2020.04.011.
[40]	Hu Y, Lin J, Fang H, et al. Targeting the MALAT1/PARP1/LIG3 complex induces DNA damage and apoptosis in multiple myeloma[J]. Leukemia, 2018, 32(10):2250-2262. doi: 10.1038/s41375-018-0104-2. pmid: 29632340
[41]	Fu S, Wang Y, Li H, et al. Regulatory Networks of LncRNA MALAT-1 in Cancer[J]. Cancer Manag Res, 2020, 12:10181-10198. doi: 10.2147/CMAR.S276022. pmid: 33116873
[42]	Liu YD, Li Y, Feng SX, et al. Long Noncoding RNAs: Potential Regulators Involved in the Pathogenesis of Polycystic Ovary Syndrome[J]. Endocrinology, 2017, 158(11):3890-3899. doi: 10.1210/en.2017-00605.
[43]	Chen Y, Chen Y, Cui X, et al. Down-regulation of MALAT1 aggravates polycystic ovary syndrome by regulating MiR-302d-3p-mediated leukemia inhibitory factor activity[J]. Life Sci, 2021, 277:119076. doi: 10.1016/j.lfs.2021.119076.
[44]	Zhao T, Pan Y, Li Q, et al. Leukemia inhibitory factor enhances the development and subsequent blastocysts quality of yak oocytes in vitro[J]. Front Vet Sci, 2022,9:997709. doi: 10.3389/fvets.2022.997709.
[45]	Kara M, Ozcan SS, Aran T, et al. Evaluation of Endometrial Receptivity by Measuring HOXA-10, HOXA-11, and Leukemia Inhibitory Factor Expression in Patients with Polycystic Ovary Syndrome[J]. Gynecol Minim Invasive Ther, 2019, 8(3):118-122. doi: 10.4103/GMIT.GMIT_112_18. pmid: 31544022
[46]	Zhang D, Tang HY, Tan L, et al. MALAT1 is involved in the pathophysiological process of PCOS by modulating TGFβ signaling in granulosa cells[J]. Mol Cell Endocrinol, 2020,499:110589. doi: 10.1016/j.mce.2019.110589.