Regulation study of ubiquitin-specific protease 39 for cell proliferation and apoptosis in colorectal cancer cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 XING Zhiyuan ¹ ,  ZHANG Fengjuan ² , WANG Zhiwei ¹

1. Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, Shandong 266000, P. R. China;
2. Department of Infection, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266042, P. R. China;

Corresponding author：

XING Zhiyuan, Email: xzyqdu@163.com

Keywords：

colorectal cancer; ubiquitin-specific peptidase 39; shRNA; cell apoptosis; targeted therapy

DOI：

10.7507/1007-9424.201805087

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective This study is aimed to determine the expression of ubiquitin-specific peptidase 39 (USP39) protein in the colorectal cancer (CRC) tissues, and the effect of silencing USP39 gene on the cell growth and cell cycle distribution of CRC cells.Methods ① The expressions of USP39 protein in CRC tissues and its paracancerous tissues were determined by immunohistochemical staining method. ② By lentiviral infection, Lv-shUSP39 (KD-1 and KD-2 group) and Lv-shCon (shCon group) were transferred into SW1116 and HCT116 cells, and cells of blank control group did not received any treatment (Con group). To determine the role of USP39 gene in cell growth, MTT assay was performed to draw growth curve, and cell cycle distribution of CRC cells in the 4 groups were determined by flow cytometer.Results ① The expression of USP39 protein was higher in CRC tissues compared to adjacent tissues (P=0.007). ② For SW1116 and HCT116 cells, the cell proliferation ability of KD-1 and KD-2 groups were remarkably decreased than those in corresponding shCon and Con groups on 3, 4, and 5-day (P<0.05). ③ Flow cytometry assay showed that, the percentage of G₀/G₁ phase cells were decreased obviously (P<0.05), while increased significantly in percentage of G₂/M phase and number of sub-G₁ phase cells in KD-1 group compared with that in the Con group and shCon group of SW1116 and HCT116 cells (P<0.05).Conclusions The expression of USP39 protein is highly expressed in CRC tissues. Knockdowning of USP39 gene can inhibit cell proliferation and promote cell apoptosis.

Citation： XING Zhiyuan, ZHANG Fengjuan, WANG Zhiwei. Regulation study of ubiquitin-specific protease 39 for cell proliferation and apoptosis in colorectal cancer cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(12): 1439-1444. doi: 10.7507/1007-9424.201805087 Copy

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4.	Kirstein MM, Lange A, Prenzler A, et al. Targeted therapies in metastatic colorectal cancer: a systematic review and assessment of currently available data. Oncologist, 2014, 19(11): 1156-1168.
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7.	van Leuken RJ, Luna-Vargas MP, Sixma TK, et al. Usp39 is essential for mitotic spindle checkpoint integrity and controls mRNA-levels of aurora B. Cell Cycle, 2008, 7(17): 2710-2719.
8.	Makarova OV, Makarov EM, Lührmann R. The 65 and 110 kDa SR-related proteins of the U4/U6.U5 tri-snRNP are essential for the assembly of mature spliceosomes. EMBO J, 2001, 20(10): 2553-2563.
9.	Gan Z, Han K, Lin S, et al. Knockdown of ubiquitin-specific peptidase 39 inhibited the growth of osteosarcoma cells and induced apoptosis in vitro. Biol Res, 2017, 50(1): 15.
10.	Huang Y, Pan XW, Li L, et al. Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation. Oncotarget, 2016, 7(16): 22016-22030.
11.	Liu S, Liu X, Wang H, et al. Lentiviral vector-mediated doxycycline-inducible USP39 shRNA or cDNA expression in triple-negative breast cancer cells. Oncol Rep, 2015, 33(5): 2477-2483.
12.	Yuan X, Sun X, Shi X, et al. USP39 promotes the growth of human hepatocellular carcinoma in vitro and in vivo. Oncol Rep, 2015, 34(2): 823-832.
13.	An Y, Yang S, Guo K, et al. Reduced USP39 expression inhibits malignant proliferation of medullary thyroid carcinoma in vitro. World J Surg Oncol, 2015, 13(1): 255.
14.	许良中, 杨文涛. 免疫组织化学反映结果的判断标准. 中国癌症杂志, 1996, 6(4): 229-231.
15.	Sun W, Yao L, Jiang B, et al. Spindle and kinetochore-associated protein 1 is overexpressed in gastric cancer and modulates cell growth. Mol Cell Biochem, 2014, 391(1-2): 167-174.
16.	Mamlouk S, Childs LH, Aust D, et al. DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer. Nat Commun, 2017, 8: 14093.
17.	Sartore-Bianchi A, Trusolino L, Martino C, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol, 2016, 17(6): 738-746.
18.	Khotskaya YB, Holla VR, Farago AF, et al. Targeting TRK family proteins in cancer. Pharmacol Ther, 2017, 173: 58-66.
19.	Wan L, Yu W, Shen E, et al. SRSF6-regulated alternative splicing that promotes tumour progression offers a therapy target for colorectal cancer. Gut, 2017, [Epub ahead of print].
20.	Allgayer H, Fulda S. An introduction to molecular targeted therapy of cancer. Adv Med Sci, 2008, 53(2): 130-138.
21.	Shih YH, Luo TY, Chiang PF, et al. EGFR-targeted micelles containing near-infrared dye for enhanced photothermal therapy in colorectal cancer. J Control Release, 2017, 258: 196-207.
22.	Augustine TA, Baig M, Sood A, et al. Telomere length is a novel predictive biomarker of sensitivity to anti-EGFR therapy in metastatic colorectal cancer. Br J Cancer, 2015, 112(2): 313-318.
23.	Fraile JM, Quesada V, Rodríguez D, et al. Deubiquitinases in cancer: new functions and therapeutic options. Oncogene, 2012, 31(19): 2373-2388.
24.	Lygerou Z, Christophides G, Séraphin B. A novel genetic screen for snRNP assembly factors in yeast identifies a conserved protein, Sad1p, also required for pre-mRNA splicing. Mol Cell Biol, 1999, 19(3): 2008-2020.
25.	Dong X, Su H, Jiang F, et al. miR-133a, directly targeted USP39, suppresses cell proliferation and predicts prognosis of gastric cancer. Oncol Lett, 2018, 15(6): 8311-8318.
26.	Xu Y, Zhu MR, Zhang JY, et al. Knockdown of ubiquitin-specific peptidase 39 inhibits the malignant progression of human renal cell carcinoma. Mol Med Rep, 2018, 17(3): 4729-4735.
27.	Yuan X, Sun X, Shi X, et al. USP39 regulates the growth of SMMC-7721 cells via FoxM1. Exp Ther Med, 2017, 13(4): 1506-1513.

1. Tilg H, Adolph TE, Gerner RR, et al. The intestinal microbiota in colorectal cancer. Cancer Cell, 2018, 33(6): 954-964.
2. Smith JJ, Garcia-Aguilar J. Advances and challenges in treatment of locally advanced rectal cancer. J Clin Oncol, 2015, 33(16): 1797-1808.
3. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet, 2014, 383(9927): 1490-1502.
4. Kirstein MM, Lange A, Prenzler A, et al. Targeted therapies in metastatic colorectal cancer: a systematic review and assessment of currently available data. Oncologist, 2014, 19(11): 1156-1168.
5. Aoyagi K, Kouhuji K, Kizaki J, et al. Molecular targeting to treat gastric cancer. World J Gastroenterol, 2014, 20(38): 13741-13755.
6. Poulin EJ, Haigis KM. No back seat for a progression event-K-RAS as a therapeutic target in CRC. Genes Dev, 2017, 31(4): 333-335.
7. van Leuken RJ, Luna-Vargas MP, Sixma TK, et al. Usp39 is essential for mitotic spindle checkpoint integrity and controls mRNA-levels of aurora B. Cell Cycle, 2008, 7(17): 2710-2719.
8. Makarova OV, Makarov EM, Lührmann R. The 65 and 110 kDa SR-related proteins of the U4/U6.U5 tri-snRNP are essential for the assembly of mature spliceosomes. EMBO J, 2001, 20(10): 2553-2563.
9. Gan Z, Han K, Lin S, et al. Knockdown of ubiquitin-specific peptidase 39 inhibited the growth of osteosarcoma cells and induced apoptosis in vitro. Biol Res, 2017, 50(1): 15.
10. Huang Y, Pan XW, Li L, et al. Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation. Oncotarget, 2016, 7(16): 22016-22030.
11. Liu S, Liu X, Wang H, et al. Lentiviral vector-mediated doxycycline-inducible USP39 shRNA or cDNA expression in triple-negative breast cancer cells. Oncol Rep, 2015, 33(5): 2477-2483.
12. Yuan X, Sun X, Shi X, et al. USP39 promotes the growth of human hepatocellular carcinoma in vitro and in vivo. Oncol Rep, 2015, 34(2): 823-832.
13. An Y, Yang S, Guo K, et al. Reduced USP39 expression inhibits malignant proliferation of medullary thyroid carcinoma in vitro. World J Surg Oncol, 2015, 13(1): 255.
14. 许良中, 杨文涛. 免疫组织化学反映结果的判断标准. 中国癌症杂志, 1996, 6(4): 229-231.
15. Sun W, Yao L, Jiang B, et al. Spindle and kinetochore-associated protein 1 is overexpressed in gastric cancer and modulates cell growth. Mol Cell Biochem, 2014, 391(1-2): 167-174.
16. Mamlouk S, Childs LH, Aust D, et al. DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer. Nat Commun, 2017, 8: 14093.
17. Sartore-Bianchi A, Trusolino L, Martino C, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol, 2016, 17(6): 738-746.
18. Khotskaya YB, Holla VR, Farago AF, et al. Targeting TRK family proteins in cancer. Pharmacol Ther, 2017, 173: 58-66.
19. Wan L, Yu W, Shen E, et al. SRSF6-regulated alternative splicing that promotes tumour progression offers a therapy target for colorectal cancer. Gut, 2017, [Epub ahead of print].
20. Allgayer H, Fulda S. An introduction to molecular targeted therapy of cancer. Adv Med Sci, 2008, 53(2): 130-138.
21. Shih YH, Luo TY, Chiang PF, et al. EGFR-targeted micelles containing near-infrared dye for enhanced photothermal therapy in colorectal cancer. J Control Release, 2017, 258: 196-207.
22. Augustine TA, Baig M, Sood A, et al. Telomere length is a novel predictive biomarker of sensitivity to anti-EGFR therapy in metastatic colorectal cancer. Br J Cancer, 2015, 112(2): 313-318.
23. Fraile JM, Quesada V, Rodríguez D, et al. Deubiquitinases in cancer: new functions and therapeutic options. Oncogene, 2012, 31(19): 2373-2388.
24. Lygerou Z, Christophides G, Séraphin B. A novel genetic screen for snRNP assembly factors in yeast identifies a conserved protein, Sad1p, also required for pre-mRNA splicing. Mol Cell Biol, 1999, 19(3): 2008-2020.
25. Dong X, Su H, Jiang F, et al. miR-133a, directly targeted USP39, suppresses cell proliferation and predicts prognosis of gastric cancer. Oncol Lett, 2018, 15(6): 8311-8318.
26. Xu Y, Zhu MR, Zhang JY, et al. Knockdown of ubiquitin-specific peptidase 39 inhibits the malignant progression of human renal cell carcinoma. Mol Med Rep, 2018, 17(3): 4729-4735.
27. Yuan X, Sun X, Shi X, et al. USP39 regulates the growth of SMMC-7721 cells via FoxM1. Exp Ther Med, 2017, 13(4): 1506-1513.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Regulation study of ubiquitin-specific protease 39 for cell proliferation and apoptosis in colorectal cancer cells

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