Hes-related family BHLH transcription factor with YRPW motif 1-activated proteasome 26S subunit, non-ATPase 14 regulates trophoblast function and endometrial angiogenesis

Zhang,Lingyun; Zhang,Shan; Chen,Fangrong

doi:10.3892/etm.2022.11403

Hes-related family BHLH transcription factor with YRPW motif 1-activated proteasome 26S subunit, non-ATPase 14 regulates trophoblast function and endometrial angiogenesis

Authors:
- Lingyun Zhang
- Shan Zhang
- Fangrong Chen
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Affiliations: Department of Obstetrics, Jiaozhou Central Hospital of Qingdao City, Qingdao, Shandong 266300, P.R. China, Community Health Service Center, Qingdao, Shandong 266300, P.R. China, Department of Obstetrics, Hainan General Hospital (Hainan Affiliated Hospital of Medical University), Haikou, Hainan 570311, P.R. China
Published online on: May 31, 2022 https://doi.org/10.3892/etm.2022.11403
Article Number: 476
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Proteasome 26S subunit, non-ATPase 14 (PSMD14) expression has been previously reported to be reduced in patients with pre-eclampsia (PE). The present study investigated the interaction network associated with the role of PSMD14 in PE. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were performed to determine the transfection efficacy following plasmid-based gene transfer of PSMD14 into HTR-8/SVneo cells. Cell proliferation was measured using an MTT assay and 5-ethynyl-2'-deoxyuridine staining. The expression of proliferation-related proteins, including Ki67 and PCNA, was determined using western blotting. Wound healing and Transwell assays were performed to measure cell invasion and migration, whilst the expression of migration-related proteins, including MMP2 and MMP9, was measured using western blotting. The angiogenesis of HUVECs following treatment with the HTR-8/SVneo cell culture supernatant was examined using tube formation assay. Following overexpression of Hes-related family BHLH transcription factor with YRPW motif 1 (HEY1) by transfection of pcDNA3.1 expression vector containing full-length human HEY1 or knockdown by transfection of shRNA plasmids targeting HEY1, the expression of HEY1 and PSMD14 was detected using RT-qPCR and western blotting. The potential interaction between HEY1 and the PSMD14 promoter was examined using dual-luciferase reporter and chromatin immunoprecipitation assays. PSMD14 overexpression was found to promote the proliferation, invasion, migration of HTR-8/SVneo cells and the angiogenesis of HUVECs following treatment with the HTR-8/SVneo cell culture supernatant, accompanied by enhanced expression of proliferation and migration-related proteins. Furthermore, the transcription factor HEY1 activated the expression of PSMD14. Knocking down HEY1 expression partially reversed the promoting effects of PSMD14 overexpression on the proliferation, invasion, migration, angiogenesis, proliferation and migration-related protein expression in trophoblasts. In conclusion, HEY1-activated PSMD14 promoted trophoblast proliferation, invasion and angiogenesis. Therefore, HEY1 and PSMD14 can be potential targets for PE treatment.

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1	Mol BWJ, Roberts CT, Thangaratinam S, Magee LA, de Groot CJM and Hofmeyr GJ: Pre-eclampsia. Lancet. 387:999–1011. 2016.PubMed/NCBI View Article : Google Scholar
2	Burton GJ, Redman CW, Roberts JM and Moffett A: Pre-eclampsia: Pathophysiology and clinical implications. BMJ. 366(l2381)2019.PubMed/NCBI View Article : Google Scholar
3	Phipps EA, Thadhani R, Benzing T and Karumanchi SA: Pre-eclampsia: Pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 15:275–289. 2019.PubMed/NCBI View Article : Google Scholar
4	Duley L, Gulmezoglu AM, Henderson-Smart DJ and Chou D: Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010(CD000025)2010.PubMed/NCBI View Article : Google Scholar
5	Warrington JP, George EM, Palei AC, Spradley FT and Granger JP: Recent advances in the understanding of the pathophysiology of preeclampsia. Hypertension. 62:666–673. 2013.PubMed/NCBI View Article : Google Scholar
6	Fisher SJ: Why is placentation abnormal in preeclampsia? Am J Obstet Gynecol. 213 (Suppl 4):S115–S22. 2015.PubMed/NCBI View Article : Google Scholar
7	Chaiworapongsa T, Chaemsaithong P, Yeo L and Romero R: Pre-eclampsia part 1: Current understanding of its pathophysiology. Nat Rev Nephrol. 10:466–480. 2014.PubMed/NCBI View Article : Google Scholar
8	Steegers EA, von Dadelszen P, Duvekot JJ and Pijnenborg R: Pre-eclampsia. Lancet. 376:631–644. 2010.PubMed/NCBI View Article : Google Scholar
9	Zou Y, Li S, Wu D, Xu Y, Wang S, Jiang Y, Liu F, Jiang Z, Qu H, Yu X, et al: Resveratrol promotes trophoblast invasion in pre-eclampsia by inducing epithelial-mesenchymal transition. J Cell Mol Med. 23:2702–2710. 2019.PubMed/NCBI View Article : Google Scholar
10	Escudero C, Puebla C, Westermeier F and Sobrevia L: Potential cell signalling mechanisms involved in differential placental angiogenesis in mild and severe pre-eclampsia. Curr Vasc Pharmacol. 7:475–85. 2009.PubMed/NCBI View Article : Google Scholar
11	Staff AC, Fjeldstad HE, Fosheim IK, Moe K, Turowski G, Johnsen GM, Alnaes-Katjavivi P and Sugulle M: Failure of physiological transformation and spiral artery atherosis: Their roles in preeclampsia. Am J Obstet Gynecol. 226 (Suppl):S895–S906. 2022.PubMed/NCBI View Article : Google Scholar
12	Virtanen A, Huttala O, Tihtonen K, Toimela T, Heinonen T and Uotila J: Angiogenic capacity in pre-eclampsia and uncomplicated pregnancy estimated by assay of angiogenic proteins and an in vitro vasculogenesis/angiogenesis test. Angiogenesis. 22:67–74. 2019.PubMed/NCBI View Article : Google Scholar
13	Xu Z, Wu C, Liu Y, Wang N, Gao S, Qiu S, Wang Z, Ding J, Zhang L, Wang H, et al: Identifying key genes and drug screening for preeclampsia based on gene expression profiles. Oncol Lett. 20:1585–1596. 2020.PubMed/NCBI View Article : Google Scholar
14	Lv J, Zhang S, Wu H, Lu J, Lu Y, Wang F, Zhao W, Zhan P, Lu J, Fang Q, et al: Deubiquitinase PSMD14 enhances hepatocellular carcinoma growth and metastasis by stabilizing GRB2. Cancer Lett. 469:22–34. 2020.PubMed/NCBI View Article : Google Scholar
15	Graham CH, Hawley TS, Hawley RG, MacDougall JR, Kerbel RS, Khoo N and Lala PK: Establishment and characterization of first trimester human trophoblast cells with extended lifespan. Exp Cell Res. 206:204–211. 1993.PubMed/NCBI View Article : Google Scholar
16	Abou-Kheir W, Barrak J, Hadadeh O and Daoud G: HTR-8/SVneo cell line contains a mixed population of cells. Placenta. 50:1–7. 2017.PubMed/NCBI View Article : Google Scholar
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
18	Abalos E, Cuesta C, Grosso AL, Chou D and Say L: Global and regional estimates of preeclampsia and eclampsia: A systematic review. Eur J Obstet Gynecol Reprod Biol. 170:1–7. 2013.PubMed/NCBI View Article : Google Scholar
19	Wallis AB, Saftlas AF, Hsia J and Atrash HK: Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987-2004. Am J Hypertens. 21:521–526. 2008.PubMed/NCBI View Article : Google Scholar
20	Sibai B, Dekker G and Kupferminc M: Pre-eclampsia. Lancet. 365:785–799. 2005.PubMed/NCBI View Article : Google Scholar
21	Abraham C and Kusheleva N: Management of Pre-eclampsia and eclampsia: A simulation. MedEdPORTAL. 15(10832)2019.PubMed/NCBI View Article : Google Scholar
22	Lin Y, Chen Y, Huang J, Chen H, Shen W, Guo W, Chen Q, Ling H and Gan X: Efficacy of premedication with intranasal dexmedetomidine on inhalational induction and postoperative emergence agitation in pediatric undergoing cataract surgery with sevoflurane. J Clin Anesth. 33:289–295. 2016.PubMed/NCBI View Article : Google Scholar
23	Yu Z, Wang J, Zhang P and Ding W: Ulinastatin attenuates vascular endothelial cell damage in pregnant women with severe pre-eclampsia. An Acad Bras Cienc. 91(e20180746)2019.PubMed/NCBI View Article : Google Scholar
24	Abbas Y, Turco MY, Burton GJ and Moffett A: Investigation of human trophoblast invasion in vitro. Hum Reprod Update. 26:501–513. 2020.PubMed/NCBI View Article : Google Scholar
25	Ridder A, Giorgione V, Khalil A and Thilaganathan B: Preeclampsia: The relationship between uterine artery blood flow and trophoblast function. Int J Mol Sci. 20(3263)2019.PubMed/NCBI View Article : Google Scholar
26	Qi L, Zhou B, Chen J, Hu W, Bai R, Ye C, Weng X and Zheng S: Significant prognostic values of differentially expressed-aberrantly methylated hub genes in breast cancer. J Cancer. 10:6618–6634. 2019.PubMed/NCBI View Article : Google Scholar
27	Zhang L, Xu H, Ma C, Zhang J, Zhao Y, Yang X, Wang S and Li D: Upregulation of deubiquitinase PSMD14 in lung adenocarcinoma (LUAD) and its prognostic significance. J Cancer. 11:2962–2971. 2020.PubMed/NCBI View Article : Google Scholar
28	Yokoyama S, Iwakami Y, Hang Z, Kin R, Zhou Y, Yasuta Y, Takahashi A, Hayakawa Y and Sakurai H: Targeting PSMD14 inhibits melanoma growth through SMAD3 stabilization. Sci Rep. 10(19214)2020.PubMed/NCBI View Article : Google Scholar
29	Luo G, Hu N, Xia X, Zhou J and Ye C: RPN11 deubiquitinase promotes proliferation and migration of breast cancer cells. Mol Med Rep. 16:331–338. 2017.PubMed/NCBI View Article : Google Scholar
30	Zuo Q, Huang S, Zou Y, Xu Y, Jiang Z, Zou S, Xu H and Sun L: The Lnc RNA SPRY4-IT1 modulates trophoblast cell invasion and migration by affecting the epithelial-mesenchymal transition. Sci Rep. 6(37183)2016.PubMed/NCBI View Article : Google Scholar
31	Xu J, Xia Y, Zhang H, Guo H, Feng K and Zhang C: Overexpression of long non-coding RNA H19 promotes invasion and autophagy via the PI3K/AKT/mTOR pathways in trophoblast cells. Biomed Pharmacother. 101:691–697. 2018.PubMed/NCBI View Article : Google Scholar
32	Ge H, Yin N, Han TL, Huang D, Chen X, Xu P, He C, Tong C and Qi H: Interleukin-27 inhibits trophoblast cell invasion and migration by affecting the epithelial-mesenchymal transition in preeclampsia. Reprod Sci. 26:928–938. 2019.PubMed/NCBI View Article : Google Scholar
33	Bai R, Kusama K, Nakamura K, Sakurai T, Kimura K, Ideta A, Aoyagi Y and Imakawa K: Down-regulation of transcription factor OVOL2 contributes to epithelial-mesenchymal transition in a noninvasive type of trophoblast implantation to the maternal endometrium. FASEB J. 32:3371–3384. 2018.PubMed/NCBI View Article : Google Scholar
34	Fragkiadaki P, Soulitzis N, Sifakis S, Koutroulakis D, Gourvas V, Vrachnis N and Spandidos DA: Downregulation of notch signaling pathway in late preterm and term placentas from pregnancies complicated by preeclampsia. PLoS One. 10(e0126163)2015.PubMed/NCBI View Article : Google Scholar
35	Yu H, Jia R, Zhao L, Song S, Gu J and Zhang H: LDB2 inhibits proliferation and migration in liver cancer cells by abrogating HEY1 expression. Oncotarget. 8:94440–94449. 2017.PubMed/NCBI View Article : Google Scholar
36	Tsung AJ, Guda MR, Asuthkar S, Labak CM, Purvis IJ, Lu Y, Jain N, Bach SE, Prasad DVR and Velpula KK: Methylation regulates HEY1 expression in glioblastoma. Oncotarget. 8:44398–44409. 2017.PubMed/NCBI View Article : Google Scholar