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Article

USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance

  • Authors:
    • Lingzhi Wang
    • Tanxiu Chen
    • Xukun Li
    • Wei Yan
    • Yanhui Lou
    • Zhihua Liu
    • Hongyan Chen
    • Zhumei Cui
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266061, P.R. China, Department of Science and Education, Jiangxi Key Laboratory of Translational Cancer Research, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China, State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beiing 100021, P.R. China, 6th Department of Internal Medicine, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
  • Pages: 277-288
    |
    Published online on: May 29, 2019
       https://doi.org/10.3892/ijo.2019.4818
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Abstract

Ubiquitin‑specific protease 39 (USP39), as one of the deubiquitinating enzymes (DUBs), exhibits aberrant an expression and has oncogenic functions in several types of cancer. However, the function and underlying molecular mechanisms of action of USP39 in ovarian cancer remain largely undetermined. The present study thus aimed to investigate whether USP39 is a promising tumor‑associated gene and whether it could be a viable target for overcoming chemotherapeutic resistance in ovarian cancer. The present study identified that USP39 was highly expressed in ovarian cancer samples with carboplatin resistance. A series of functional assays revealed that the knockdown of USP39 in ES2 and SKOV3 cells significantly decreased cell proliferation, induced cell cycle arrest at the G2/M phase and impaired the cell colony formation ability. USP39 deficiency enhanced the carboplatin‑induced apoptosis of the SKOV3 cells via the activation of poly‑ADP ribose polymerase and caspase‑3. USP39 knockdown led to the inhibition of cell migration and invasion. The opposite effects were observed when USP39 was overexpressed in the ES2 and SKOV3 cells. In vivo animal models revealed that the subcutaneous transplantation and intraperitoneal injection of USP39‑overexpressing ES2 cells increased tumor burden with or without treatment with carboplatin. However, the knockdown of USP39 suppressed SKOV3 cell growth in vivo. Mechanistic analyses also demonstrated that USP39 induced the phosphorylation of extracellular signal‑regulated kinase and AKT and increased the expression of epidermal growth factor receptor and cyclin B1. Collectively, the findings of this study suggest that USP39 may paly a vital role in regulating ovarian cancer malignant phenotypes and carboplatin resistance. Therefore, USP39 may prove to be a promising therapeutic target for patients with ovarian cancer.
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View References

1 

Cheng JQ, Jiang X, Fraser M, Li M, Dan HC, Sun M and Tsang BK: Role of X-linked inhibitor of apoptosis protein in chemoresistance in ovarian cancer: Possible involvement of the phosphoinositide-3 kinase/Akt pathway. Drug Resist Updat. 5:131–146. 2002. View Article : Google Scholar

2 

Russo A, Czarnecki AA, Dean M, Modi DA, Lantvit DD, Hardy L, Baligod S, Davis DA, Wei JJ and Burdette JE: PTEN loss in the fallopian tube induces hyperplasia and ovarian tumor formation. Oncogene. 37:1976–1990. 2018. View Article : Google Scholar : PubMed/NCBI

3 

van Zyl B, Tang D and Bowden NA: Biomarkers of platinum resistance in ovarian cancer: What can we use to improve treatment. Endocr Relat Cancer. 25:R303–R318. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Ricciardelli C, Lokman NA, Ween MP and Oehler MK: Women in cancer thematic review: Ovarian cancer-peritoneal cell interactions promote extracellular matrix processing. Endocr Relat Cancer. 23:T155–T168. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Li KY, Zhang J, Jiang LC, Zhang B, Xia CP, Xu K, Chen HY, Yang QZ, Liu SW and Zhu H: Knockdown of USP39 by lentivirus-mediated RNA interference suppresses the growth of oral squamous cell carcinoma. Cancer Biomark. 16:137–144. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Zhao Y, Zhang B, Lei Y, Sun J, Zhang Y, Yang S and Zhang X: Knockdown of USP39 induces cell cycle arrest and apoptosis in melanoma. Tumour Biol. 37:13167–13176. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Ríos Y, Melmed S, Lin S and Liu NA: Zebrafish usp39 mutation leads to rb1 mRNA splicing defect and pituitary lineage expansion. PLoS Genet. 7:e10012712011. View Article : Google Scholar : PubMed/NCBI

8 

Fraile JM, Manchado E, Lujambio A, Quesada V, Campos-Iglesias D, Webb TR, Lowe SW, López-Otín C and Freije JM: USP39 Deubiquitinase Is Essential for KRAS Oncogene-driven Cancer. J Biol Chem. 292:4164–4175. 2017. View Article : Google Scholar : PubMed/NCBI

9 

An Y, Yang S, Guo K, Ma B and Wang Y: Reduced USP39 expression inhibits malignant proliferation of medullary thyroid carcinoma in vitro. World J Surg Oncol. 13:2552015. View Article : Google Scholar : PubMed/NCBI

10 

Huang Y, Pan XW, Li L, Chen L, Liu X, Lu JL, Zhu XM, Huang H, Yang QW, Ye JQ, et al: Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation. Oncotarget. 7:22016–22030. 2016.PubMed/NCBI

11 

Wang H, Ji X, Liu X, Yao R, Chi J, Liu S, Wang Y, Cao W and Zhou Q: Lentivirus-mediated inhibition of USP39 suppresses the growth of breast cancer cells in vitro. Oncol Rep. 30:2871–2877. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Li Y, Kong Y, Zhou Z, Chen H, Wang Z, Hsieh YC, Zhao D, Zhi X, Huang J, Zhang J, et al: The HECTD3 E3 ubiquitin ligase facilitates cancer cell survival by promoting K63-linked polyu-biquitination of caspase-8. Cell Death Dis. 4:e9352013. View Article : Google Scholar

13 

Shu T, Li Y, Wu X, Li B and Liu Z: Down-regulation of HECTD3 by HER2 inhibition makes serous ovarian cancer cells sensitive to platinum treatment. Cancer Lett. 411:65–73. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar

15 

Wu X, Luo Q, Zhao P, Chang W, Wang Y, Shu T, Ding F, Li B and Liu Z: MGMT-activated DUB3 stabilizes MCL1 and drives chemoresistance in ovarian cancer. Proc Natl Acad Sci USA. 116:2961–2966. 2019. View Article : Google Scholar : PubMed/NCBI

16 

Ueno M, Shiomi T, Mochizuki S, Chijiiwa M, Shimoda M, Kanai Y, Kataoka F, Hirasawa A, Susumu N, Aoki D, et al: ADAM9 is over-expressed in human ovarian clear cell carcinomas and suppresses cisplatin-induced cell death. Cancer Sci. 109:471–482. 2018. View Article : Google Scholar :

17 

Xu Y, Miao C, Jin C, Qiu C, Li Y, Sun X, Gao M, Lu N and Kong B: SUSD2 promotes cancer metastasis and confers cisplatin resistance in high grade serous ovarian cancer. Exp Cell Res. 363:160–170. 2018. View Article : Google Scholar : PubMed/NCBI

18 

Longoria TC and Tewari KS: Pharmacokinetic drug evaluation of niraparib for the treatment of ovarian cancer. Expert Opin Drug Metab Toxicol. 14:543–550. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Ricciardelli C, Lokman NA, Sabit I, Gunasegaran K, Bonner WM, Pyragius CE, Macpherson AM and Oehler MK: Novel ex vivo ovarian cancer tissue explant assay for prediction of chemosensitivity and response to novel therapeutics. Cancer Lett. 421:51–58. 2018. View Article : Google Scholar : PubMed/NCBI

20 

Wei W, Giulia F, Luffer S, Kumar R, Wu B, Tavallai M, Bekele RT and Birrer MJ: How can molecular abnormalities influence our clinical approach. Ann Oncol. 28:viii16–viii24. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Zhang P, Zhang P, Shi B, Zhou M, Jiang H, Zhang H, Pan X, Gao H, Sun H and Li Z: Galectin-1 overexpression promotes progression and chemoresistance to cisplatin in epithelial ovarian cancer. Cell Death Dis. 5:e9912014. View Article : Google Scholar : PubMed/NCBI

22 

Birkbak NJ, Li Y, Pathania S, Greene-Colozzi A, Dreze M, Bowman-Colin C, Sztupinszki Z, Krzystanek M, Diossy M, Tung N, et al: Overexpression of BLM promotes DNA damage and increased sensitivity to platinum salts in triple-negative breast and serous ovarian cancers. Ann Oncol. 29:903–909. 2018. View Article : Google Scholar : PubMed/NCBI

23 

Wang Y, Chen D, Qian H, Tsai YS, Shao S, Liu Q, Dominguez D and Wang Z: The splicing factor RBM4 controls apoptosis, proliferation, and migration to suppress tumor progression. Cancer Cell. 26:374–389. 2014. View Article : Google Scholar : PubMed/NCBI

24 

No authors listed. RBM4-regulated alternative splicing suppresses tumorigenesis. Cancer Discov. 4:12532014. View Article : Google Scholar

25 

Chen L, Luo C, Shen L, Liu Y, Wang Q, Zhang C, Guo R, Zhang Y, Xie Z, Wei N, et al: SRSF1 Prevents DNA Damage and Promotes Tumorigenesis through Regulation of DBF4B Pre-mRNA Splicing. Cell Rep. 21:3406–3413. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Anczuków O, Akerman M, Cléry A, Wu J, Shen C, Shirole NH, Raimer A, Sun S, Jensen MA, Hua Y, et al: SRSF1-regulated alternative splicing in breast cancer. Mol Cell. 60:105–117. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Gan Z, Han K, Lin S, Hu H, Shen Z and Min D: Knockdown of ubiquitin-specific peptidase 39 inhibited the growth of osteo-sarcoma cells and induced apoptosis in vitro. Biol Res. 50:152017. View Article : Google Scholar

28 

Pan Z, Pan H, Zhang J, Yang Y, Liu H, Yang Y, Huang G, Ni J, Huang J and Zhou W: Lentivirus mediated silencing of ubiquitin specific peptidase 39 inhibits cell proliferation of human hepato-cellular carcinoma cells in vitro. Biol Res. 48:182015. View Article : Google Scholar

29 

Tuan Anh HL, Tran PT, Thao DT, Trang DT, Dang NH, Van Cuong P, Kiem PV, Minh CV and Lee JH: Degalactotigonin, a steroidal glycoside from solanum nigrum, induces apoptosis and cell cycle arrest via inhibiting the EGFR signaling pathways in pancreatic cancer cells. BioMed Res Int. 2018:31209722018. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Wang L, Chen T, Li X, Yan W, Lou Y, Liu Z, Chen H and Cui Z: USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance. Int J Oncol 55: 277-288, 2019.
APA
Wang, L., Chen, T., Li, X., Yan, W., Lou, Y., Liu, Z. ... Cui, Z. (2019). USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance. International Journal of Oncology, 55, 277-288. https://doi.org/10.3892/ijo.2019.4818
MLA
Wang, L., Chen, T., Li, X., Yan, W., Lou, Y., Liu, Z., Chen, H., Cui, Z."USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance". International Journal of Oncology 55.1 (2019): 277-288.
Chicago
Wang, L., Chen, T., Li, X., Yan, W., Lou, Y., Liu, Z., Chen, H., Cui, Z."USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance". International Journal of Oncology 55, no. 1 (2019): 277-288. https://doi.org/10.3892/ijo.2019.4818
Copy and paste a formatted citation
x
Spandidos Publications style
Wang L, Chen T, Li X, Yan W, Lou Y, Liu Z, Chen H and Cui Z: USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance. Int J Oncol 55: 277-288, 2019.
APA
Wang, L., Chen, T., Li, X., Yan, W., Lou, Y., Liu, Z. ... Cui, Z. (2019). USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance. International Journal of Oncology, 55, 277-288. https://doi.org/10.3892/ijo.2019.4818
MLA
Wang, L., Chen, T., Li, X., Yan, W., Lou, Y., Liu, Z., Chen, H., Cui, Z."USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance". International Journal of Oncology 55.1 (2019): 277-288.
Chicago
Wang, L., Chen, T., Li, X., Yan, W., Lou, Y., Liu, Z., Chen, H., Cui, Z."USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance". International Journal of Oncology 55, no. 1 (2019): 277-288. https://doi.org/10.3892/ijo.2019.4818
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