Wild-type p53-induced phosphatase 1 (WIP1) regulates the proliferation of swine Sertoli cells through P53
Bingyuan Wang A * , Mingrui Zhang A B * , Jingjing Che A , Kui Li A , Yulian Mu A C and Zhiguo Liu A CA Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
B College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
C Corresponding authors. Email: mouyulian@caas.cn; liuzhiguo@caas.cn
Reproduction, Fertility and Development 32(18) 1350-1356 https://doi.org/10.1071/RD20215
Submitted: 19 August 2020 Accepted: 29 October 2020 Published: 8 December 2020
Abstract
Wild-type p53-induced phosphatase 1 (WIP1) plays an oncogenic function by increasing cell proliferation in various cancer types. Deficiency in WIP1 expression leads to male infertility, possibly by impairing the blood–testis barrier and spermatogenesis. However, how WIP1 functions in the Sertoli cells to affect male reproduction remains unclear. Thus, in the present study we used a swine Sertoli cell line to investigate whether WIP1 regulated the proliferation of Sertoli cells to participate in male reproduction. The WIP1 inhibitor GSK2830371, WIP1-short interference (si) RNAs and an upstream microRNA (miR-16) were used to inhibit the expression of WIP1, after which the proliferation of swine Sertoli cells, P53 expression and the levels of P53 phosphorylation were determined. Inhibiting WIP1 expression suppressed swine Sertoli cell proliferation, increased P53 expression and increased levels of P53 phosphorylation. In addition, overexpression of miR-16 in swine Sertoli cells resulted in a decrease in WIP1 expression and increases in both P53 expression and P53 phosphorylation. Together, these findings suggest that WIP1 positively regulates the proliferation of swine Sertoli cells by inhibiting P53 phosphorylation, and the miR-16 is likely also involved by targeting WIP1.
Keywords: miR-16, P53, proliferation, swine Sertoli cells, wild-type p53-induced phosphatase 1 (WIP1).
References
Alves, M. G., Rato, L., Carvalho, R. A., Moreira, P. I., Socorro, S., and Oliveira, P. F. (2013). Hormonal control of Sertoli cell metabolism regulates spermatogenesis. Cell. Mol. Life Sci. 70, 777–793.| Hormonal control of Sertoli cell metabolism regulates spermatogenesis.Crossref | GoogleScholarGoogle Scholar | 23011766PubMed |
Bonci, D., Coppola, V., Musumeci, M., Addario, A., Giuffrida, R., Memeo, L., D’Urso, L., Pagliuca, A., Biffoni, M., Labbaye, C., Bartucci, M., Muto, G., Peschle, C., and De Maria, R. (2008). The miR-15a–miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat. Med. 14, 1271–1277.
| The miR-15a–miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities.Crossref | GoogleScholarGoogle Scholar | 18931683PubMed |
Chen, S. R., and Liu, Y. X. (2015). Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling. Reproduction 149, R159–R167.
| Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling.Crossref | GoogleScholarGoogle Scholar | 25504872PubMed |
Chen, Z., Wang, L., Yao, D., Yang, T., Cao, W. M., Dou, J., Pang, J. C., Guan, S., Zhang, H., Yu, Y., Zhao, Y., Wang, Y., Xu, X., Shi, Y., Patel, R., Zhang, H., Vasudevan, S. A., Liu, S., Yang, J., and Nuchtern, J. G. (2016). Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis. Sci. Rep. 6, 38011.
| Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis.Crossref | GoogleScholarGoogle Scholar | 27991505PubMed |
Cheng, C. Y., and Mruk, D. D. (2012). The blood–testis barrier and its implications for male contraception. Pharmacol. Rev. 64, 16–64.
| The blood–testis barrier and its implications for male contraception.Crossref | GoogleScholarGoogle Scholar | 22039149PubMed |
Choi, J., Appella, E., and Donehower, L. A. (2000). The structure and expression of the murine wildtype p53-induced phosphatase 1 (Wip1) gene. Genomics 64, 298–306.
| The structure and expression of the murine wildtype p53-induced phosphatase 1 (Wip1) gene.Crossref | GoogleScholarGoogle Scholar | 10756097PubMed |
Choi, J., Nannenga, B., Demidov, O. N., Bulavin, D. V., Cooney, A., Brayton, C., Zhang, Y., Mbawuike, I. N., Bradley, A., Appella, E., and Donehower, L. A. (2002). Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control. Mol. Cell. Biol. 22, 1094–1105.
| Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control.Crossref | GoogleScholarGoogle Scholar | 11809801PubMed |
Chojnacka, K., Zarzycka, M., and Mruk, D. D. (2016). Biology of the Sertoli cell in the fetal, pubertal, and adult mammalian testis. Results Probl. Cell Differ. 58, 225–251.
| Biology of the Sertoli cell in the fetal, pubertal, and adult mammalian testis.Crossref | GoogleScholarGoogle Scholar | 27300181PubMed |
Filipponi, D., Muller, J., Emelyanov, A., and Bulavin, D. V. (2013). Wip1 controls global heterochromatin silencing via ATM/BRCA1-dependent DNA methylation. Cancer Cell 24, 528–541.
| Wip1 controls global heterochromatin silencing via ATM/BRCA1-dependent DNA methylation.Crossref | GoogleScholarGoogle Scholar | 24135283PubMed |
Gerber, J., Heinrich, J., and Brehm, R. (2016). Blood–testis barrier and Sertoli cell function: lessons from SCCx43KO mice. Reproduction 151, R15–R27.
| Blood–testis barrier and Sertoli cell function: lessons from SCCx43KO mice.Crossref | GoogleScholarGoogle Scholar | 26556893PubMed |
Gilmartin, A. G., Faitg, T. H., Richter, M., Groy, A., Seefeld, M. A., Darcy, M. G., Peng, X., Federowicz, K., Yang, J., Zhang, S. Y., Minthorn, E., Jaworski, J. P., Schaber, M., Martens, S., McNulty, D. E., Sinnamon, R. H., Zhang, H., Kirkpatrick, R. B., Nevins, N., Cui, G., Pietrak, B., Diaz, E., Jones, A., Brandt, M., Schwartz, B., Heerding, D. A., and Kumar, R. (2014). Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction. Nat. Chem. Biol. 10, 181–187.
| Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction.Crossref | GoogleScholarGoogle Scholar | 24390428PubMed |
Hickson, J. A., Fong, B., Watson, P. H., and Watson, A. J. (2007). PP2Cdelta (Ppm1d, WIP1), an endogenous inhibitor of p38 MAPK, is regulated along with Trp53 and Cdkn2a following p38 MAPK inhibition during mouse preimplantation development. Mol. Reprod. Dev. 74, 821–834.
| PP2Cdelta (Ppm1d, WIP1), an endogenous inhibitor of p38 MAPK, is regulated along with Trp53 and Cdkn2a following p38 MAPK inhibition during mouse preimplantation development.Crossref | GoogleScholarGoogle Scholar | 17219434PubMed |
Jiang, X. H., Bukhari, I., Zheng, W., Yin, S., Wang, Z., Cooke, H. J., and Shi, Q. H. (2014). Blood–testis barrier and spermatogenesis: lessons from genetically-modified mice. Asian J. Androl. 16, 572–580.
| Blood–testis barrier and spermatogenesis: lessons from genetically-modified mice.Crossref | GoogleScholarGoogle Scholar | 24713828PubMed |
Le Guezennec, X., Brichkina, A., Huang, Y. F., Kostromina, E., Han, W., and Bulavin, D. V. (2012). Wip1-dependent regulation of autophagy, obesity, and atherosclerosis. Cell Metab. 16, 68–80.
| Wip1-dependent regulation of autophagy, obesity, and atherosclerosis.Crossref | GoogleScholarGoogle Scholar | 22768840PubMed |
Leem, J., Kim, J. S., and Oh, J. S. (2018). WIP1 phosphatase suppresses the DNA damage response during G2/prophase arrest in mouse oocytes. Biol. Reprod. 99, 798–805.
| WIP1 phosphatase suppresses the DNA damage response during G2/prophase arrest in mouse oocytes.Crossref | GoogleScholarGoogle Scholar | 29733326PubMed |
Lu, X., Nannenga, B., and Donehower, L. A. (2005). PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev. 19, 1162–1174.
| PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints.Crossref | GoogleScholarGoogle Scholar | 15870257PubMed |
Lu, Z. W., Wen, D., Wei, W. J., Han, L. T., Xiang, J., Wang, Y. L., Wang, Y., Liao, T., and Ji, Q. H. (2020). Silencing of PPM1D inhibits cell proliferation and invasion through the p38 MAPK and p53 signaling pathway in papillary thyroid carcinoma. Oncol. Rep. 43, 783–794.
| Silencing of PPM1D inhibits cell proliferation and invasion through the p38 MAPK and p53 signaling pathway in papillary thyroid carcinoma.Crossref | GoogleScholarGoogle Scholar | 31922231PubMed |
Ma, C., Song, H., Guan, K., Zhou, J., Xia, X., and Li, F. (2016). Characterization of swine testicular cell line as immature porcine Sertoli cell line. In Vitro Cell. Dev. Biol. Anim. 52, 427–433.
| Characterization of swine testicular cell line as immature porcine Sertoli cell line.Crossref | GoogleScholarGoogle Scholar | 26744029PubMed |
Napoletano, F., Gibert, B., Yacobi-Sharon, K., Vincent, S., Favrot, C., Mehlen, P., Girard, V., Teil, M., Chatelain, G., Walter, L., Arama, E., and Mollereau, B. (2017). p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis. PLoS Genet. 13, e1007024.
| p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.Crossref | GoogleScholarGoogle Scholar | 28945745PubMed |
Niu, P., Wei, Y., Gao, Q., Zhang, X., Hu, Y., Qiu, Y., Mu, Y., and Li, K. (2019). Male fertility potential molecular mechanisms revealed by iTRAQ-based quantitative proteomic analysis of the epididymis from Wip1(–/–) mice. OMICS 23, 54–66.
| Male fertility potential molecular mechanisms revealed by iTRAQ-based quantitative proteomic analysis of the epididymis from Wip1(–/–) mice.Crossref | GoogleScholarGoogle Scholar | 30629479PubMed |
Oghabi Bakhshaiesh, T., Majidzadeh, A. K., and Esmaeili, R. (2017). Wip1: a candidate phosphatase for cancer diagnosis and treatment. DNA Repair (Amst.) 54, 63–66.
| Wip1: a candidate phosphatase for cancer diagnosis and treatment.Crossref | GoogleScholarGoogle Scholar | 28385459PubMed |
Pechackova, S., Burdova, K., Benada, J., Kleiblova, P., Jenikova, G., and Macurek, L. (2016). Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3. Oncotarget 7, 14458–14475.
| Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3.Crossref | GoogleScholarGoogle Scholar | 26883108PubMed |
Qian, Y. C., Xie, Y. X., Wang, C. S., Shi, Z. M., Jiang, C. F., Tang, Y. Y., Qian, X., Wang, L., and Jiang, B. H. (2020). Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis. Asian J. Androl. 22, 414–421.
| Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis.Crossref | GoogleScholarGoogle Scholar | 31489847PubMed |
Schito, M. L., Demidov, O. N., Saito, S., Ashwell, J. D., and Appella, E. (2006). Wip1 phosphatase-deficient mice exhibit defective T cell maturation due to sustained p53 activation. J. Immunol. 176, 4818–4825.
| Wip1 phosphatase-deficient mice exhibit defective T cell maturation due to sustained p53 activation.Crossref | GoogleScholarGoogle Scholar | 16585576PubMed |
Sun, B., Hu, X., Liu, G., Ma, B., Xu, Y., Yang, T., Shi, J., Yang, F., Li, H., Zhang, L., and Zhao, Y. (2014). Phosphatase Wip1 negatively regulates neutrophil migration and inflammation. J. Immunol. 192, 1184–1195.
| Phosphatase Wip1 negatively regulates neutrophil migration and inflammation.Crossref | GoogleScholarGoogle Scholar | 24395919PubMed |
Wang, B., Li, D., Sidler, C., Rodriguez-Juarez, R., Singh, N., Heyns, M., Ilnytskyy, Y., Bronson, R. T., and Kovalchuk, O. (2015). A suppressive role of ionizing radiation-responsive miR-29c in the development of liver carcinoma via targeting WIP1. Oncotarget 6, 9937–9950.
| A suppressive role of ionizing radiation-responsive miR-29c in the development of liver carcinoma via targeting WIP1.Crossref | GoogleScholarGoogle Scholar | 25888625PubMed |
Wang, P., Zhao, Y., Liu, K., Liu, X., Liang, J., Zhou, H., Wang, Z., Zhou, Z., and Xu, N. (2019). Wip1 cooperates with KPNA2 to modulate the cell proliferation and migration of colorectal cancer via a p53-dependent manner. J. Cell. Biochem. 120, 15709–15718.
| Wip1 cooperates with KPNA2 to modulate the cell proliferation and migration of colorectal cancer via a p53-dependent manner.Crossref | GoogleScholarGoogle Scholar | 31127650PubMed |
Wei, Y., Gao, Q., Niu, P., Xu, K., Qiu, Y., Hu, Y., Liu, S., Zhang, X., Yu, M., Liu, Z., Wang, B., Mu, Y., and Li, K. (2019). Integrative proteomic and phosphoproteomic profiling of testis from Wip1 phosphatase-knockout mice: insights into mechanisms of reduced fertility. Mol. Cell. Proteomics 18, 216–230.
| Integrative proteomic and phosphoproteomic profiling of testis from Wip1 phosphatase-knockout mice: insights into mechanisms of reduced fertility.Crossref | GoogleScholarGoogle Scholar | 30361445PubMed |
Yi, W., Hu, X., Chen, Z., Liu, L., Tian, Y., Chen, H., Cong, Y. S., Yang, F., Zhang, L., Rudolph, K. L., Zhang, Z., Zhao, Y., and Ju, Z. (2015). Phosphatase Wip1 controls antigen-independent B-cell development in a p53-dependent manner. Blood 126, 620–628.
| Phosphatase Wip1 controls antigen-independent B-cell development in a p53-dependent manner.Crossref | GoogleScholarGoogle Scholar | 26012568PubMed |
Zhan, X. H., Xu, Q. Y., Tian, R., Yan, H., Zhang, M., Wu, J., Wang, W., and He, J. (2017). MicroRNA16 regulates glioma cell proliferation, apoptosis and invasion by targeting Wip1–ATM–p53 feedback loop. Oncotarget 8, 54788–54798.
| MicroRNA16 regulates glioma cell proliferation, apoptosis and invasion by targeting Wip1–ATM–p53 feedback loop.Crossref | GoogleScholarGoogle Scholar | 28903382PubMed |
Zhang, X., Wan, G., Mlotshwa, S., Vance, V., Berger, F. G., Chen, H., and Lu, X. (2010). Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway. Cancer Res. 70, 7176–7186.
| Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway.Crossref | GoogleScholarGoogle Scholar | 20668064PubMed |
Zhang, Y., Sun, H., He, G., Liu, A., Wang, F., and Wang, L. (2014). WIP1 regulates the proliferation and invasion of nasopharyngeal carcinoma in vitro. Tumour Biol. 35, 7651–7657.
| WIP1 regulates the proliferation and invasion of nasopharyngeal carcinoma in vitro.Crossref | GoogleScholarGoogle Scholar | 24801909PubMed |
Zhu, Y. H., and Bulavin, D. V. (2012). Wip1-dependent signaling pathways in health and diseases. Prog. Mol. Biol. Transl. Sci. 106, 307–325.
| Wip1-dependent signaling pathways in health and diseases.Crossref | GoogleScholarGoogle Scholar | 22340722PubMed |
Zhu, Y., Demidov, O. N., Goh, A. M., Virshup, D. M., Lane, D. P., and Bulavin, D. V. (2014). Phosphatase WIP1 regulates adult neurogenesis and WNT signaling during aging. J. Clin. Invest. 124, 3263–3273.
| Phosphatase WIP1 regulates adult neurogenesis and WNT signaling during aging.Crossref | GoogleScholarGoogle Scholar | 24911145PubMed |