https://doi.org/10.4081/ejtm.2024.12516
Linc00513 sponges miR-7 to modulate TGF-β signaling in azoospermia
Submitted: 27 March 2024
Accepted: 5 June 2024
Published: 1 July 2024
Accepted: 5 June 2024
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Azoospermia, or the complete absence of sperm in the ejaculate, affects about 1% of men worldwide and is a significant fertility challenge. This study investigates Linc00513, a long non-coding RNA, and its potential role in regulating the TGF-β signaling pathway, a key player in spermatogenesis, in the context of azoospermia. We show that Linc00513 expression is significantly lower in testicular tissues from azoospermic patients than in HS1 controls. Linc00513 interacts directly with microRNA-7 (miR-7) via complementary base pairing, acting as a competing endogenous RNA (ceRNA). This interaction effectively inhibits miR-7's inhibitory action on the TGF-β receptor 1 (TGFBR1), a critical component of the TGF-β signaling cascade. Downregulating Linc00513 reduces TGFBR1 repression and increases TGF-β signaling in azoospermic testes. Functional assays with spermatogonial cell lines support these findings. Silencing Linc00513 leads to increased cell proliferation and decreased apoptosis, similar to TGF-β inhibition. Overexpression of miR-7 inhibits the effects of Linc00513 on TGF-β signaling. Our study sheds new light on how Linc00513, miR-7, and the TGF-β signaling pathway interact in azoospermia. Linc00513 regulates TGFBR1 expression and thus influences spermatogonial cell fate by acting as a miR-7 ceRNA. These findings identify a potential therapeutic target for azoospermia treatment, paving the way for future research into restoring fertility in affected individuals.
Karavolos S. Diagnosing" his" infertility: men's experiences and reflections on the diagnosis of azoospermia. 2016, Newcastle University.
Demyashkin GA, Borovaya TG, Andreeva YY, et al. An experimental approach to comprehend the influence of platelet rich growth factors on spermatogenesis. Int J Radiat Biol 2022;98:1330-43.
DOI: https://doi.org/10.1080/09553002.2022.2047820
Demyashkin GA, Kogan E, Demura T, et al. Immunohistochemical analysis of spermatogenesis in patients with SARS-CoV-2 Invasion in different age groups. Curr Issues Mol Biol 2023;45:2444-51.
DOI: https://doi.org/10.3390/cimb45030159
Anderson GM. Men’s Experience of miscarriage: coping with the loss of a life and future. PhD Thesis, Liberty University; 2023.
Najmi M, Ayari MA, Sadeghsalehi H, et al. Estimating the dissolution of anticancer drugs in supercritical carbon dioxide with a stacked machine learning model. Pharmaceutics 2022;14:1632.
DOI: https://doi.org/10.3390/pharmaceutics14081632
Usman M, Li A, Wu D, et al. The functional role of lncRNAs as ceRNAs in both ovarian processes and associated diseases. Noncoding RNA Res 2023;9:165-77.
DOI: https://doi.org/10.1016/j.ncrna.2023.11.008
Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol 2021;22:96-118.
DOI: https://doi.org/10.1038/s41580-020-00315-9
O'Leary S, Armstrong DT, Robertson SA. Transforming growth factor-β (TGFβ) in porcine seminal plasma. Reprod Fertil Dev 2011;23:748-58.
DOI: https://doi.org/10.1071/RD11001
Massagué J, Sheppard D. TGF-β signaling in health and disease. Cell 2023;186:4007-37.
DOI: https://doi.org/10.1016/j.cell.2023.07.036
Mirzaei H, Faghihloo E. Viruses as key modulators of the TGF-β pathway; a double-edged sword involved in cancer. Rev Med Virol 2018;28:e1967.
DOI: https://doi.org/10.1002/rmv.1967
Oatley JM, Brinster RL. Regulation of spermatogonial stem cell self-renewal in mammals. Annu Rev Cell Dev Biol 2008;24:263-86.
DOI: https://doi.org/10.1146/annurev.cellbio.24.110707.175355
van Rooij E, Olson EN. MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat Rev Drug Discov 2012;11:860-72.
DOI: https://doi.org/10.1038/nrd3864
Rezaei M, Rahmani E, Khouzani SJ, et al., Role of artificial intelligence in the diagnosis and treatment of diseases. Kindle 2023;3:1-160.
Yang Z, Zhang X, Chen Z, Hu C. Effect of Wuzi Yanzong on reproductive hormones and TGF-β1/smads signal pathway in rats with oligoasthenozoospermia. Evid Based Complement Alternat Med 2019;2019:7628125.
DOI: https://doi.org/10.1155/2019/7628125
Isaksen A, Trippl M. Exogenously led and policy-supported new path development in peripheral regions: Analytical and synthetic routes. Econ Geogr 2017;93:436-57.
DOI: https://doi.org/10.1080/00130095.2016.1154443
Nishimura H, L'Hernault SW. Spermatogenesis. Curr Biol 2017;27:R988-94.
DOI: https://doi.org/10.1016/j.cub.2017.07.067
Zhao L, Yao C, Xing X, et al. Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells. Nat Commun 2020;11:5683.
DOI: https://doi.org/10.1038/s41467-020-19414-4
Martirosyan YO, Silachev DN, Nazarenko TA, et al. Stem-cell-derived extracellular vesicles: unlocking new possibilities for treating diminished ovarian reserve and premature ovarian insufficiency. Life (Basel) 2023;13:2247.
DOI: https://doi.org/10.3390/life13122247
Ahmed K, LaPierre MP, Gasser E, et al. Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility. J Clin Invest 2017;127:1061-74.
DOI: https://doi.org/10.1172/JCI90031
Rastgar Rezaei Y, Zarezadeh R, Nikanfar S, et al. microRNAs in the pathogenesis of non-obstructive azoospermia: the underlying mechanisms and therapeutic potentials. Syst Biol Reprod Med 2021;67:337-53.
DOI: https://doi.org/10.1080/19396368.2021.1951890
Cerván-Martín M, Castilla JA, Palomino-Morales RJ, Carmona FD. Genetic Landscape of Nonobstructive Azoospermia and New Perspectives for the Clinic. J Clin Med 2020;9:300.
DOI: https://doi.org/10.3390/jcm9020300
Nie H, Wang Y, Liao Z, et al. The function and mechanism of circular RNAs in gastrointestinal tumours. Cell Prolif 2020;53:e12815.
DOI: https://doi.org/10.1111/cpr.12815
Wang JM, Li ZF, Yang WX. What does androgen receptor signaling pathway in sertoli cells during normal spermatogenesis tell us? Front Endocrinol 2022;13:838858.
DOI: https://doi.org/10.3389/fendo.2022.838858
Alm E, Arkin AP. Biological networks. Curr Opinion Structural Biol 2003;13:193-202.
DOI: https://doi.org/10.1016/S0959-440X(03)00031-9
Wu W, Qin Y, Li Z, et al. Genome-wide microRNA expression profiling in idiopathic non-obstructive azoospermia: significant up-regulation of miR-141, miR-429 and miR-7-1-3p. Hum Reprod 2013;28:1827-36.
DOI: https://doi.org/10.1093/humrep/det099
Al-Naqshbandi AA, Nafee Darogha S, Asaaf Maulood K. Genotypic and allelic prevalence of the TGF- Β1 +869 C/T SNP and their relationship to seminogram in infertile males. Rep Biochem Mol Biol 2023;12:318-31.
DOI: https://doi.org/10.61186/rbmb.12.2.318
Mehta P, Joshi M, Singh R. TGF-β signaling in testicular development, spermatogenesis, and infertility, molecular signaling in spermatogenesis and male infertility. 2019, CRC Press. p. 105-115.
DOI: https://doi.org/10.1201/9780429244216-11
Quaife NM, Chothani S, Schulz JF, et al. LINC01013 is a determinant of fibroblast activation and encodes a novel fibroblast-activating micropeptide. J Cardiovasc Transl Res 2023;16:77-85.
DOI: https://doi.org/10.1007/s12265-022-10288-z
Papoutsoglou P, Pineau R, Leroux R, et al. TGFβ-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma. EMBO Rep 2024;25:1022-54.
DOI: https://doi.org/10.1038/s44319-024-00075-z
Zhang W, Zhang Y, Zhao M, et al. MicroRNA expression profiles in the seminal plasma of nonobstructive azoospermia patients with different histopathologic patterns. Fertil Steril 2021;115:1197-211.
DOI: https://doi.org/10.1016/j.fertnstert.2020.11.020
Cannarella R, Bertelli M, Condorelli RA, Vet al. Analysis of 29 targeted genes for non-obstructive azoospermia: the relationship between genetic testing and testicular histology. World J Mens Health 2023;41:422-33.
DOI: https://doi.org/10.5534/wjmh.220009
How to Cite
Etezadi, A., Akhtare, A., Asadikalameh, Z., Aghaei, Z. H., Panahinia, P., Arman, M., Abtahian, A., Khorasani, F. F., & Hazari, V. (2024). Linc00513 sponges miR-7 to modulate TGF-β signaling in azoospermia. European Journal of Translational Myology, 34(3). https://doi.org/10.4081/ejtm.2024.12516
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