TRIM27 regulates the expression of PDCD4 by the ubiquitin‑proteasome pathway in ovarian and endometrial cancer cells

Yu,Huayun; Wan,Lu; Tang,Zhongyun; Yao,Chenchen; Zhang,Derui; Jiang,Mengmeng; Wang,Chongli; Liu,Yuqiu; Xue,Chenyue; Wang,Xishuang; Shi,Yongyu; Zhang,Lining; Wang,Xiaoyan; Wei,Zengtao

doi:10.3892/or.2022.8331

TRIM27 regulates the expression of PDCD4 by the ubiquitin‑proteasome pathway in ovarian and endometrial cancer cells

Authors:
- Huayun Yu
- Lu Wan
- Zhongyun Tang
- Chenchen Yao
- Derui Zhang
- Mengmeng Jiang
- Chongli Wang
- Yuqiu Liu
- Chenyue Xue
- Xishuang Wang
- Yongyu Shi
- Lining Zhang
- Xiaoyan Wang
- Zengtao Wei
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Affiliations: Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, P.R. China, Department of Gynecology and Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China
Published online on: May 16, 2022 https://doi.org/10.3892/or.2022.8331
Article Number: 120

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Abstract

Programmed cell death 4 (PDCD4) is regarded as an important tumor suppressor that is lowly expressed or deleted in numerous human types of cancer, including ovarian and endometrial cancer. Tripartite motif‑containing 27 (TRIM27) is closely related to the occurrence and development of tumors and is highly expressed in numerous types of cancer such as ovarian and endometrial cancer. PDCD4 can be degraded through ubiquitination, while TRIM27 has the E3 ubiquitin ligase activity. However, whether TRIM27 may regulate the expression of PDCD4 by ubiquitination effect remains unclear. In the present study, the expression of PDCD4 and TRIM27 in different ovarian and endometrial cancer cell lines was detected by reverse transcription‑quantitative PCR (RT‑qPCR), western blotting and immunocytochemistry. The impact of TRIM27 overexpression and knockdown on PDCD4 expression and the effective mechanism of TRIM27 regulating PDCD4 expression were also investigated in vitro by RT‑qPCR, western blotting, co‑immunoprecipitation assay, Transwell migration and Matrigel invasion assays. The results showed that the expression of TRIM27 and PDCD4 had a negative association at the protein level, and the distribution of TRIM27 and PDCD4 proteins had a phenomenon of co‑localization in different ovarian and endometrial cancer cell lines. TRIM27 promoted the degradation of PDCD4 through the ubiquitin‑proteasome pathway. To sum up, TRIM27 could increase the migration and invasion of ovarian and endometrial cancer cells by promoting the ubiquitination and degradation of PDCD4. The present findings may provide a new target for the treatment of ovarian and endometrial cancer.

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1	Visser NCM, Reijnen C, Massuger LFAG, Nagtegaal ID, Bulten J and Pijnenborg JMA: Accuracy of endometrial sampling in endometrial carcinoma: A Systematic review and meta-analysis. Obstet Gynecol. 130:803–813. 2017. View Article : Google Scholar
2	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, ParkinD M, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
3	Hinchcliff EM, Bednar EM, Lu KH and Rauh-Hain JA: Disparities in gynecologic cancer genetics evaluation. Gynecol Oncol. 153:184–191. 2019. View Article : Google Scholar
4	Schlichter U, Burk O, Worpenberg S and Klempnauer KH: The chicken Pdcd4 gene is regulated by v-Myb. Oncogene. 20:231–239. 2001. View Article : Google Scholar : PubMed/NCBI
5	Jansen AP, Camalier CE, Stark C and Colburn NH: Characterization of programmed cell death 4 in multiple human cancers reveals a novel enhancer of drug sensitivity. Mol Cancer Ther. 3:103–110. 2004.PubMed/NCBI
6	Wang Q and Yang HS: The role of Pdcd4 in tumour suppression and protein translation. Biol Cell. May 28–2018.(Epub ahead of print). View Article : Google Scholar
7	Nieves-Alicea R, Colburn NH, Simeone AM and Tari AM: Programmed cell death 4 inhibits breast cancer cell invasion by increasing tissue inhibitor of metalloproteinases-2 expression. Breast Cancer Res Treat. 114:203–209. 2009. View Article : Google Scholar
8	Wei N, Liu SS, Chan KK and Ngan HY: Tumour suppressive function and modulation of programmed cell death 4 (PDCD4) in ovarian cancer. PLoS One. 7:e303112012. View Article : Google Scholar : PubMed/NCBI
9	Wei ZT, Zhang X, Wang XY, Gao F, Zhou CJ, Zhu FL, Wang Q, Gao Q, Ma CH, Sun WS, et al: PDCD4 inhibits the malignant phenotype of ovarian cancer cells. Cancer Sci. 100:1408–1413. 2009. View Article : Google Scholar
10	Wang X, Wei Z, Gao F, Zhang X, Zhou C, Zhu F, Wang Q, Gao Q, Ma C, Sun W, et al: Expression and prognostic significance of PDCD4 in human epithelial ovarian carcinoma. Anti Res. 28:2991–2996. 2008.
11	Liu Y, Sun H, Mao H, Gao M, Tan X, Li Y, Li Y, Muloye GM, Zhang L, Wang X and Wei Z: Expression of tumor suppressor programmed cell death 4 in endometrioid endometrial carcinomas and clinicopathological significance. Oncol Lett. 15:9369–9376. 2018.
12	Zhang X, Wang X, Song X, Liu C, Shi Y, Wang Y, Afonja O, Ma C, Chen YH and Zhang L: Programmed cell death 4 enhances chemosensitivity of ovarian cancer cells by activating death receptor pathway in vitro and in vivo. Cancer Sci. 101:2163–2170. 2010. View Article : Google Scholar
13	Gao F, Wang X, Zhu F, Wang Q, Zhang X, Guo C, Zhou C, Ma C, Sun W, Zhang Y, et al: PDCD4 gene silencing in gliomas is associated with 5′CpG island methylation and unfavourable prognosis. J Cell Mol Med. 13:4257–4267. 2009. View Article : Google Scholar : PubMed/NCBI
14	Sun J, Yong J and Zhang H: microRNA-93, upregulated in serum of nasopharyngeal carcinoma patients, promotes tumor cell proliferation by targeting PDCD4. Exp Ther Med. 19:2579–2587. 2020.PubMed/NCBI
15	Zhou XH, Chai HX, Bai M and Zhang Z: LncRNA-GAS5 regulates PDCD4 expression and mediates myocardial infarction-induced cardiomyocytes apoptosis via targeting MiR-21. Cell Cycle. 19:1363–1377. 2020. View Article : Google Scholar : PubMed/NCBI
16	Cui H, Wang Q, Lei Z, Feng M, Zhao Z, Wang Y and Wei G: DTL promotes cancer progression by PDCD4 ubiquitin-dependent degradation. J Exp Clin Cancer Res. 38:3502019. View Article : Google Scholar : PubMed/NCBI
17	Townson SM, Kang K, Lee AV and Oesterreich S: Novel role of the RET finger protein in estrogen receptor-mediated transcription in MCF-7 cells. Biochem Biophys Res Commun. 349:540–548. 2006. View Article : Google Scholar : PubMed/NCBI
18	Micale L, Chaignat E, Fusco C, Reymond A and Merla G: The tripartite motif: Structure and function. Adv Exp Med Biol. 770:11–25. 2012. View Article : Google Scholar
19	Joazeiro CA and Weissman AM: RING finger proteins: Mediators of ubiquitin ligase activity. Cell. 102:549–552. 2000. View Article : Google Scholar
20	Harbers M, Nomura T, Ohno S and Ishii S: Intracellular localization of the Ret finger protein depends on a functional nuclear export signal and protein kinase C activation. J Biol Chem. 276:48596–48607. 2001. View Article : Google Scholar : PubMed/NCBI
21	Iwakoshi A, Murakumo Y, Kato T, Kitamura A, Mii S, Saito S, Yatabe Y and Takahashi M: RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations. Pathol Int. 62:324–330. 2012. View Article : Google Scholar
22	Tezel GG, Uner A, Yildiz I, Guler G and Takahashi M: RET finger protein expression in invasive breast carcinoma: Relationship between RFP and ErbB2 expression. Pathol Res Pract. 205:403–408. 2009. View Article : Google Scholar
23	Ma Y, Wei Z, Bast RC Jr, Wang Z, Li Y, Gao M, Liu Y and Wang X, Guo C, Zhang L and Wang X: Downregulation of TRIM27 expression inhibits the proliferation of ovarian cancer cells in vitro and in vivo. Lab Invest. 96:37–48. 2016. View Article : Google Scholar
24	Tsukamoto H, Kato T, Enomoto A, Nakamura N, Shimono Y, Jijiwa M, Asai N, Murakumo Y, Shibata K, Kikkawa F and Takahashi M: Expression of Ret finger protein correlates with outcomes in endometrial cancer. Cancer Sci. 100:1895–1901. 2009. View Article : Google Scholar
25	Horio M, Kato T, Mii S, Enomoto A, Asai M, Asai N, Murakumo Y, Shibata K, Kikkawa F and Takahashi M: Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer. Cancer Med. 1:218–229. 2012. View Article : Google Scholar : PubMed/NCBI
26	Cai X, Srivastava S, Sun Y, Li Z, Wu H, Zuvela-Jelaska L, Li J, Salamon RS, Backer JM and Skolnik EY: Tripartite motif containing protein 27 negatively regulates CD4 T cells by ubiquitinating and inhibiting the class II PI3K-C2β. Proc Natl Acad Sci USA. 108:20072–20077. 2011. View Article : Google Scholar : PubMed/NCBI
27	Zheng Q, Hou J, Zhou Y, Yang Y, Xie B and Cao X: Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27. Cell Res. 25:1121–1136. 2015. View Article : Google Scholar : PubMed/NCBI
28	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. View Article : Google Scholar : PubMed/NCBI
29	Böhm M Sawicka K, Siebrasse JP, Brehmer-Fastnacht A, Peters R and Klempnauer KH: The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA. Oncogene. 22:4905–4910. 2003. View Article : Google Scholar
30	Matsuhashi S, Manirujjaman M, Hamajima H and Ozaki I: Control mechanisms of the tumor suppressor PDCD4: Expression and functions. Int J Mol Sci. 20:23042019. View Article : Google Scholar
31	Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A and Lund AH: Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem. 283:1026–1033. 2008. View Article : Google Scholar : PubMed/NCBI
32	Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH, Sherman NE and Pagano M: S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science. 314:467–4671. 2006. View Article : Google Scholar : PubMed/NCBI
33	Mallette FA and Richard S: K48-linked ubiquitination and protein degradation regulate 53BP1 recruitment at DNA damage sites. Cell Res. 22:1221–1223. 2012. View Article : Google Scholar : PubMed/NCBI
34	Metcalf JL, Bradshaw PS, Komosa M, Greer SN, Stephen Meyn M and Ohh M: K63-Ubiquitylation of VHL by SOCS1 mediates DNA double-strand break repair. Oncogene. 33:1055–1065. 2014. View Article : Google Scholar : PubMed/NCBI
35	Joung H, Eom GH, Choe N, Lee HM, Ko JH, Kwon DH, Nam YS, Min H, Shin S, Kook J, et al: Ret finger protein mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. Cell Signal. 26:2240–2248. 2014. View Article : Google Scholar
36	Zurek B, Schoultz I, Neerincx A, Napolitano LM, Birkner K, Bennek E, Sellge G, Lerm M, Meroni G, Söderholm JD and Kufer TA: TRIM27 negatively regulates NOD2 by ubiquitination and proteasomal degradation. PLoS One. 7:e412552012. View Article : Google Scholar : PubMed/NCBI
37	Hao YH, Doyle JM, Ramanathan S, Gomez TS, Jia D, Xu M, Chen ZJ, Billadeau DD, Rosen MK and Potts PR: Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination. Cell. 152:1051–1064. 2013. View Article : Google Scholar
38	Lipkowitz S and Weissman AM: RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nat Rev Cancer. 11:629–643. 2011. View Article : Google Scholar : PubMed/NCBI