LncRNA LOC102176306 plays important roles in goat testicular development

in Reproduction
Authors:
Shi-Yu An Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China

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Zi-Fei Liu Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China

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El-Samahy M A Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China

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Ming-Tian Deng Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China

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Xiao-Xiao Gao Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China

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Ya-Xu Liang Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China

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Chen-Bo Shi Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China

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Zhi-Hai Lei College of veterinary medicine, Nanjing Agricultural University, Nanjing, China

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Feng Wang Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China

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Guo-Min Zhang Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China
College of veterinary medicine, Nanjing Agricultural University, Nanjing, China

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Correspondence should be addressed to G-M Zhang; Email: zhangguomin@njau.edu.cn
DOI:
https://doi.org/10.1530/REP-20-0568
Volume/Issue:
Volume 161: Issue 5
Page Range:
523–537
Article Type:
Research Article
Online Publication Date:
May 2021
Copyright:
© 2021 Society for Reproduction and Fertility 2021
Restricted access
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Long ncRNAs regulate a complex array of fundamental biological processes, while its molecular regulatory mechanism in Leydig cells (LCs) remains unclear. In the present study, we established the lncRNA LOC102176306/miR-1197-3p/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) regulatory network by bioinformatic prediction, and investigated its roles in goat LCs. We found that lncRNA LOC102176306 could efficiently bind to miR-1197-3p and regulate PPARGC1A expression in goat LCs. Downregulation of lncRNA LOC102176306 significantly supressed testosterone (T) synthesis and ATP production, decreased the activities of antioxidant enzymes and mitochondrial complex I and complex III, caused the loss of mitochondrial membrane potential, and inhibited the proliferation of goat LCs by decreasing PPARGC1A expression, while these effects could be restored by miR-1197-3p inhibitor treatment. In addition, miR-1197-3p mimics treatment significantly alleviated the positive effects of lncRNA LOC102176306 overexpression on T and ATP production, antioxidant capacity and proliferation of goat LCs. Taken together, lncRNA LOC102176306 functioned as a sponge for miR-1197-3p to maintain PPARGC1A expression, thereby affecting the steroidogenesis, cell proliferation and oxidative stress of goat LCs. These findings extend our understanding of the molecular mechanisms of T synthesis, cell proliferation and oxidative stress of LCs.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

  • Aghazadeh Y, Zirkin BR & Papadopoulos V 2015 Pharmacological regulation of the cholesterol transport machinery in steroidogenic cells of the testis. Vitamins & Hormones 98 189–227. (https://doi.org/10.1016/bs.vh.2014.12.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ambros V 2004 The functions of animal microRNAs. Nature 431 350–355. (https://doi.org/10.1038/nature02871)

  • An SY, Zhang GM, Liu ZF, Zhou C, Yang PC & Wang F 2019 MiR-1197-3p regulates testosterone secretion in goat Leydig cells via targeting PPARGC1A. Gene 710 131–139. (https://doi.org/10.1016/j.gene.2019.05.057)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Andric SA & Kostic TS 2019 Regulation of Leydig cell steroidogenesis: intriguing network of signaling pathways and mitochondrial signalosome. Current Opinion in Endocrine & Metabolic Research 6 7–20. (https://doi.org/10.1016/j.coemr.2019.03.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ayer A, Gourlay CW & Dawes IW 2014 Cellular redox homeostasis, reactive oxygen species and replicative ageing in Saccharomyces cerevisiae. FEMS Yeast Research 14 60–72. (https://doi.org/10.1111/1567-1364.12114)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Balaban RS, Nemoto S & Finkel T 2005 Mitochondria, oxidants, and aging. Cell 120 483–495. (https://doi.org/10.1016/j.cell.2005.02.001)

  • Beattie MC, Adekola L, Papadopoulos V, Chen H & Zirkin BR 2015 Leydig cell aging and hypogonadism. Experimental Gerontology 68 87–91. (https://doi.org/10.1016/j.exger.2015.02.014)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chan SH, Wu KL, Chang AY, Tai MH & Chan JY 2009 Oxidative impairment of mitochondrial electron transport chain complexes in rostral ventrolateral medulla contributes to neurogenic hypertension. Hypertension 53 217–227. (https://doi.org/10.1161/HYPERTENSIONAHA.108.116905)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chen H, Guo X, Xiao X, Ye L, Huang Y, Lu C & Su Z 2019 Identification and functional characterization of microRNAs in rat Leydig cells during development from the progenitor to the adult stage. Molecular & Cellular Endocrinology 493 110453. (https://doi.org/10.1016/j.mce.2019.110453)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cheng J, Fu J & Zhou Z 2005 The mechanism of manganese-induced inhibition of steroidogenesis in rat primary Leydig cells. Toxicology 211 1–11. (https://doi.org/10.1016/j.tox.2005.01.020)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cui Y, Chen R, Ma L, Yang W, Chen M, Zhang Y, Yu S, Dong W, Zeng W & Lan X et al. 2020 miR-205 expression elevated With EDS Treatment and Induced Leydig Cell Apoptosis by Targeting RAP2B via the PI3K/AKT Signaling Pathway. Frontiers in Cell & Developmental Biology 8 448. (https://doi.org/10.3389/fcell.2020.00448)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Deng M, Liu Z, Ren C, Zhang G, Pang J, Zhang Y, Wang F & Wan Y 2018 Long noncoding RNAs exchange during zygotic genome activation in goat. Biology of Reproduction 99 707–717. (https://doi.org/10.1093/biolre/ioy118)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fa S, Pogrmic-Majkic K, Samardzija D, Hrubik J, Glisic B, Kovacevic R & Andric N 2015 HBCDD-induced sustained reduction in mitochondrial membrane potential, ATP and steroidogenesis in peripubertal rat Leydig cells. Toxicology & Applied Pharmacology 282 20–29. (https://doi.org/10.1016/j.taap.2014.11.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gak IA, Radovic SM, Dukic AR, Janjic MM, Stojkov-Mimic NJ, Kostic TS & Andric SA 2015 Stress triggers mitochondrial biogenesis to preserve steroidogenesis in Leydig cells. Biochimica & Biophysica Acta 1853 2217–2227. (https://doi.org/10.1016/j.bbamcr.2015.05.030)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gao X, Ye J, Yang C, Zhang K, Li X, Luo L, Ding J, Li Y, Cao H & Ling Y et al. 2017 Screening and evaluating of long noncoding RNAs in the puberty of goats. BMC Genomics 18 164. (https://doi.org/10.1186/s12864-017-3578-9)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gao X, Zhu M, An S, Liang Y, Yang H, Pang J, Liu Z, Zhang G & Wang F 2020 Long non-coding RNA LOC105611671 modulates fibroblast growth factor 9 (FGF9) expression by targeting oar-miR-26a to promote testosterone biosynthesis in Hu sheep. Reproduction, Fertility, & Development 32 373–382. (https://doi.org/10.1071/RD19116)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Guil S & Esteller M 2015 RNA-RNA interactions in gene regulation: the coding and noncoding players. Trends in Biochemical Sciences 40 248–256. (https://doi.org/10.1016/j.tibs.2015.03.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Guo YX, Zhang GM, Yao XL, Tong R, Cheng CY, Zhang TT, Wang ST, Yang H & Wang F 2019 Effects of nitric oxide on steroidogenesis and apoptosis in goat luteinized granulosa cells. Theriogenology 126 55–62. (https://doi.org/10.1016/j.theriogenology.2018.12.007)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Haider SG 2007 Leydig cell steroidogenesis: unmasking the functional importance of mitochondria. Endocrinology 148 2581–2582. (https://doi.org/10.1210/en.2007-0330)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hales DB, Allen JA, Shankara T, Janus P, Buck S, Diemer T & Hales KH 2005 Mitochondrial function in Leydig cell steroidogenesis. Annals of the New York Academy of Sciences 1061 120–134. (https://doi.org/10.1196/annals.1336.014)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hao S, Wang L, Zhao K, Zhu X & Ye F 2019 Rs1894720 polymorphism in MIAT increased susceptibility to age-related hearing loss by modulating the activation of miR-29b/SIRT1/PGC-1alpha signaling. Journal of Cellular Biochemistry 120 4975–4986. (https://doi.org/10.1002/jcb.27773)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hescot S, Slama A, Lombes A, Paci A, Remy H, Leboulleux S, Chadarevian R, Trabado S, Amazit L & Young J et al. 2013 Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect in human adrenocortical cells. Endocrine-Related Cancer 20 371–381. (https://doi.org/10.1530/ERC-12-0368)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hwang GS, Wang SW, Tseng WM, Yu CH & Wang PS 2007 Effect of hypoxia on the release of vascular endothelial growth factor and testosterone in mouse TM3 Leydig cells. American Journal of Physiology. Endocrinology & Metabolism 292 E1763–E1769. (https://doi.org/10.1152/ajpendo.00611.2006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ipsa E, Cruzat VF, Kagize JN, Yovich JL & Keane KN 2019 Growth hormone and insulin-like growth factor action in reproductive tissues. Frontiers in Endocrinology 10 777. (https://doi.org/10.3389/fendo.2019.00777)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kong Y, Lu Z, Liu P, Liu Y, Wang F, Liang EY, Hou FF & Liang M 2019 Long noncoding RNA: genomics and relevance to physiology. Comprehensive Physiology 9 933–946. (https://doi.org/10.1002/cphy.c180032)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li J, Tian H, Yang J & Gong Z 2016 Long noncoding RNAs regulate cell growth, proliferation, and apoptosis. DNA & Cell Biology 35 459–470. (https://doi.org/10.1089/dna.2015.3187)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ling YH, Zheng Q, Li YS, Sui MH, Wu H, Zhang YH, Chu MX, Ma YH, Fang FG & Xu LN 2019 Identification of lncRNAs by RNA sequencing analysis During in vivo pre-implantation developmental transformation in the goat. Frontiers in Genetics 10 1040. (https://doi.org/10.3389/fgene.2019.01040)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu Z, Zhang G, Deng M, Yang H, Pang J, Cai Y, Wan Y & Wang F 2020 Inhibition of lysine-specific histone demethylase 1A results in meiotic aberration during oocyte maturation in vitro in goats. Theriogenology 143 168–178. (https://doi.org/10.1016/j.theriogenology.2019.12.011)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Long J, Badal SS, Ye Z, Wang Y, Ayanga BA, Galvan DL, Green NH, Chang BH, Overbeek PA & Danesh FR 2016 Long noncoding RNA Tug1 regulates mitochondrial bioenergetics in diabetic nephropathy. Journal of Clinical Investigation 126 4205–4218. (https://doi.org/10.1172/JCI87927)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lv Y, Dong Y, Wang Y, Zhu Q, Li L, Li X, Lin Z, Fan L & Ge RS 2019 Benzyl butyl phthalate non-linearly affects rat Leydig cell development during puberty. Toxicology Letters 314 53–62. (https://doi.org/10.1016/j.toxlet.2019.07.016)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Medar MLJ, Marinkovic DZ, Kojic Z, Becin AP, Starovlah IM, Kravic-Stevovic T, Andric SA & Kostic TS 2020 Dependence of Leydig cell's mitochondrial physiology on luteinizing hormone signaling. Life 11 19. (https://doi.org/10.3390/life11010019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Medja F, Allouche S, Frachon P, Jardel C, Malgat M, Mousson de Camaret B, Slama A, Lunardi J, Mazat JP & Lombes A 2009 Development and implementation of standardized respiratory chain spectrophotometric assays for clinical diagnosis. Mitochondrion 9 331–339. (https://doi.org/10.1016/j.mito.2009.05.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Merry CR, Forrest ME, Sabers JN, Beard L, Gao XH, Hatzoglou M, Jackson MW, Wang Z, Markowitz SD & Khalil AM 2015 DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer. Human Molecular Genetics 24 6240–6253. (https://doi.org/10.1093/hmg/ddv343)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Midzak AS, Chen H, Aon MA, Papadopoulos V & Zirkin BR 2011 ATP synthesis, mitochondrial function, and steroid biosynthesis in rodent primary and tumor Leydig cells. Biology of Reproduction 84 976–985. (https://doi.org/10.1095/biolreprod.110.087460)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Miller WL 2013 Steroid hormone synthesis in mitochondria. Molecular & Cellular Endocrinology 379 62–73. (https://doi.org/10.1016/j.mce.2013.04.014)

  • Murphy MP 2009 How mitochondria produce reactive oxygen species. Biochemical Journal 417 1–13. (https://doi.org/10.1042/BJ20081386)

  • Murugesan P, Balaganesh M, Balasubramanian K & Arunakaran J 2007 Effects of polychlorinated biphenyl (aroclor 1254) on steroidogenesis and antioxidant system in cultured adult rat Leydig cells. Journal of Endocrinology 192 325–338. (https://doi.org/10.1677/joe.1.06874)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Murugesan P, Muthusamy T, Balasubramanian K & Arunakaran J 2008 Polychlorinated biphenyl (aroclor 1254) inhibits testosterone biosynthesis and antioxidant enzymes in cultured rat Leydig cells. Reproductive Toxicology 25 447–454. (https://doi.org/10.1016/j.reprotox.2008.04.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Qiannan E, Wang C, Gu X, Gan X, Zhang X, Wang S, Ma J, Zhang L, Zhang R & Su L 2020 Competitive endogenous RNA (ceRNA) regulation network of lncRNA-miRNA-mRNA during the process of the nickel-induced steroidogenesis disturbance in rat Leydig cells. Toxicology in Vitro 63 104721 .

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Radovic SM, Starovlah IM, Capo I, Miljkovic D, Nef S, Kostic TS & Andric SA 2019 Insulin/IGF1 signaling regulates the mitochondrial biogenesis markers in steroidogenic cells of prepubertal testis, but not ovary. Biology of Reproduction 100 253–267. (https://doi.org/10.1093/biolre/ioy177)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rao J, Li J, Liu Y, Lu P, Sun X, Sugumaran PK & Zhu D 2012 The key role of PGC-1alpha in mitochondrial biogenesis and the proliferation of pulmonary artery vascular smooth muscle cells at an early stage of hypoxic exposure. Molecular & Cellular Biochemistry 367 9–18. (https://doi.org/10.1007/s11010-012-1313-z)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Roy VK, Verma R & Krishna A 2017 Carnitine-mediated antioxidant enzyme activity and Bcl2 expression involves peroxisome proliferator-activated receptor-gamma coactivator-1alpha in mouse testis. Reproduction, Fertility, & Development 29 1057–1063. (https://doi.org/10.1071/RD15336)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Salmena L, Poliseno L, Tay Y, Kats L & Pandolfi PP 2011 A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146 353–358. (https://doi.org/10.1016/j.cell.2011.07.014)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B & Ideker T 2003 Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Research 13 2498–2504. (https://doi.org/10.1101/gr.1239303)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sreerangaraja Urs DB, Wu WH, Komrskova K, Postlerova P, Lin YF, Tzeng CR & Kao SH 2020 Mitochondrial function in modulating human granulosa cell steroidogenesis and female fertility. International Journal of Molecular Sciences 21 3592. (https://doi.org/10.3390/ijms21103592)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Su Z, Xiong H, Pang J, Lin H, Lai L, Zhang H, Zhang W & Zheng Y 2019 LncRNA AW112010 promotes mitochondrial biogenesis and hair cell survival: implications for age-related hearing loss. Oxidative Medicine & Cellular Longevity 2019 6150148. (https://doi.org/10.1155/2019/6150148)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tian T, Lv X, Pan G, Lu Y, Chen W, He W, Lei X, Zhang H, Liu M & Sun S et al. 2019 Long noncoding RNA MPRL promotes mitochondrial fission and cisplatin chemosensitivity via disruption of pre-miRNA processing. Clinical Cancer Research 25 3673–3688. (https://doi.org/10.1158/1078-0432.CCR-18-2739)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang KC & Chang HY 2011 Molecular mechanisms of long noncoding RNAs. Molecular Cell 43 904–914. (https://doi.org/10.1016/j.molcel.2011.08.018)

  • Wang Y, Chen F, Ye L, Zirkin B & Chen H 2017 Steroidogenesis in Leydig cells: effects of aging and environmental factors. Reproduction 154 R111–R122. (https://doi.org/10.1530/REP-17-0064)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wichman L, Somasundaram S, Breindel C, Valerio DM, McCarrey JR, Hodges CA & Khalil AM 2017 Dynamic expression of long noncoding RNAs reveals their potential roles in spermatogenesis and fertility. Biology of Reproduction 97 313–323. (https://doi.org/10.1093/biolre/iox084)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wu H, Liu B, Chen Z, Li G & Zhang Z 2020 MSC-induced lncRNA HCP5 drove fatty acid oxidation through miR-3619-5p/AMPK/PGC1alpha/CEBPB axis to promote stemness and chemo-resistance of gastric cancer. Cell Death & Disease 11 233. (https://doi.org/10.1038/s41419-020-2426-z)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ye L, Su ZJ & Ge RS 2011 Inhibitors of testosterone biosynthetic and metabolic activation enzymes. Molecules 16 9983–10001. (https://doi.org/10.3390/molecules16129983)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang GM, An SY, El-Samahy MA, Zhang YL, Wan YJ, Wang ZY, Xiao SH, Meng FX, Wang F & Lei ZH 2019 Suppression of miR-1197-3p attenuates H2O2-induced apoptosis of goat luteinized granulosa cells via targeting PPARGC1A. Theriogenology 132 72–82. (https://doi.org/10.1016/j.theriogenology.2019.04.008) H2O2

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang Q, Ma XF, Dong MZ, Tan J, Zhang J, Zhuang LK, Liu SS & Xin YN 2020 MiR-30b-5p regulates the lipid metabolism by targeting PPARGC1A in Huh-7 cell line. Lipids in Health & Disease 19 76. (https://doi.org/10.1186/s12944-020-01261-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang Y, Yang H, Han L, Li F, Zhang T, Pang J, Feng X, Ren C, Mao S & Wang F 2017 Long noncoding RNA expression profile changes associated with dietary energy in the sheep testis during sexual maturation. Scientific Reports 7 5180. (https://doi.org/10.1038/s41598-017-05443-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhu X, Li H, Wu Y, Zhou J, Yang G, Wang W, Kang D & Ye S 2019 CREB-upregulated lncRNA MEG3 promotes hepatic gluconeogenesis by regulating miR-302a-3p-CRTC2 axis. Journal of Cellular Biochemistry 120 4192–4202. (https://doi.org/10.1002/jcb.27706)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zirkin BR & Papadopoulos V 2018 Leydig cells: formation, function, and regulation. Biology of Reproduction 99 101–111. (https://doi.org/10.1093/biolre/ioy059)