LncRNA LOC102176306 plays important roles in goat testicular development

in Reproduction
View More View Less
  • 1 Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China
  • 2 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
  • 3 College of veterinary medicine, Nanjing Agricultural University, Nanjing, China

Correspondence should be addressed to G-M Zhang; Email: zhangguomin@njau.edu.cn
Restricted access

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.

Supplementary Materials

    • Table S1. Candidate PPARGC1A-associated lncRNAs from sequencing datasets of goat oocytes
    • Table S2. Candidate miR-1197-3p-targeted lncRNAs from sequencing datasets of goat oocytes.

 

     An official journal of

    Society for Reproduction and Fertility

 

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 102 102 99
Full Text Views 14 14 14
PDF Downloads 23 23 23
  • Aghazadeh Y, Zirkin BR & Papadopoulos V 2015 Pharmacological regulation of the cholesterol transport machinery in steroidogenic cells of the testis. Vitamins & Hormones 98 189227. (https://doi.org/10.1016/bs.vh.2014.12.006)

    • Search Google Scholar
    • Export Citation
  • Ambros V 2004 The functions of animal microRNAs. Nature 431 350355. (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 131139. (https://doi.org/10.1016/j.gene.2019.05.057)

    • 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 6 720. (https://doi.org/10.1016/j.coemr.2019.03.001)

    • 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 6072. (https://doi.org/10.1111/1567-1364.12114)

    • Search Google Scholar
    • Export Citation
  • Balaban RS, Nemoto S & Finkel T 2005 Mitochondria, oxidants, and aging. Cell 120 483495. (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 8791. (https://doi.org/10.1016/j.exger.2015.02.014)

    • 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 217227. (https://doi.org/10.1161/HYPERTENSIONAHA.108.116905)

    • 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)

    • 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 211 111. (https://doi.org/10.1016/j.tox.2005.01.020)

    • 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)

    • 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 707717. (https://doi.org/10.1093/biolre/ioy118)

    • 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 2029. (https://doi.org/10.1016/j.taap.2014.11.001)

    • 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 22172227. (https://doi.org/10.1016/j.bbamcr.2015.05.030)

    • 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)

    • 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 373382. (https://doi.org/10.1071/RD19116)

    • 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 248256. (https://doi.org/10.1016/j.tibs.2015.03.001)

    • 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 5562. (https://doi.org/10.1016/j.theriogenology.2018.12.007)

    • Search Google Scholar
    • Export Citation
  • Haider SG 2007 Leydig cell steroidogenesis: unmasking the functional importance of mitochondria. Endocrinology 148 25812582. (https://doi.org/10.1210/en.2007-0330)

    • 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 120134. (https://doi.org/10.1196/annals.1336.014)

    • 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 49754986. (https://doi.org/10.1002/jcb.27773)

    • 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 371381. (https://doi.org/10.1530/ERC-12-0368)

    • 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 E1763E1769. (https://doi.org/10.1152/ajpendo.00611.2006)

    • 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)

    • 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 933946. (https://doi.org/10.1002/cphy.c180032)

    • 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 459470. (https://doi.org/10.1089/dna.2015.3187)

    • 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)

    • 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 168178. (https://doi.org/10.1016/j.theriogenology.2019.12.011)

    • 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 42054218. (https://doi.org/10.1172/JCI87927)

    • 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 5362. (https://doi.org/10.1016/j.toxlet.2019.07.016)

    • 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)

    • 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 331339. (https://doi.org/10.1016/j.mito.2009.05.001)

    • 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 62406253. (https://doi.org/10.1093/hmg/ddv343)

    • 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 976985. (https://doi.org/10.1095/biolreprod.110.087460)

    • Search Google Scholar
    • Export Citation
  • Miller WL 2013 Steroid hormone synthesis in mitochondria. Molecular & Cellular Endocrinology 379 6273. (https://doi.org/10.1016/j.mce.2013.04.014)

    • Search Google Scholar
    • Export Citation
  • Murphy MP 2009 How mitochondria produce reactive oxygen species. Biochemical Journal 417 113. (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 325338. (https://doi.org/10.1677/joe.1.06874)

    • 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 447454. (https://doi.org/10.1016/j.reprotox.2008.04.003)

    • 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 .

    • 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 253267. (https://doi.org/10.1093/biolre/ioy177)

    • 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 367 918. (https://doi.org/10.1007/s11010-012-1313-z)

    • 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 10571063. (https://doi.org/10.1071/RD15336)

    • 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 353358. (https://doi.org/10.1016/j.cell.2011.07.014)

    • 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 24982504. (https://doi.org/10.1101/gr.1239303)

    • 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)

    • 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)

    • 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 36733688. (https://doi.org/10.1158/1078-0432.CCR-18-2739)

    • Search Google Scholar
    • Export Citation
  • Wang KC & Chang HY 2011 Molecular mechanisms of long noncoding RNAs. Molecular Cell 43 904914. (https://doi.org/10.1016/j.molcel.2011.08.018)

    • Search Google Scholar
    • Export Citation
  • Wang Y, Chen F, Ye L, Zirkin B & Chen H 2017 Steroidogenesis in Leydig cells: effects of aging and environmental factors. Reproduction 154 R111R122. (https://doi.org/10.1530/REP-17-0064)

    • 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 313323. (https://doi.org/10.1093/biolre/iox084)

    • 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)

    • Search Google Scholar
    • Export Citation
  • Ye L, Su ZJ & Ge RS 2011 Inhibitors of testosterone biosynthetic and metabolic activation enzymes. Molecules 16 998310001. (https://doi.org/10.3390/molecules16129983)

    • 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 7282. (https://doi.org/10.1016/j.theriogenology.2019.04.008) H2O2

    • 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)

    • 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)

    • 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 41924202. (https://doi.org/10.1002/jcb.27706)

    • Search Google Scholar
    • Export Citation
  • Zirkin BR & Papadopoulos V 2018 Leydig cells: formation, function, and regulation. Biology of Reproduction 99 101111. (https://doi.org/10.1093/biolre/ioy059)

    • Search Google Scholar
    • Export Citation