Expressions of mRNA and Protein of CDK8 and TGF-β1 in Colorectal Cancer and Its Relation to Clinicopathological Features_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 WUDuo ¹ ,  XUDa-fang ¹ , ZHAOQun ² ,  YAOChun ¹ , ZHANGXiu-mei ³

1. Department of Gastrointestinal Surgery, Xinhua People's Hospital Affiliated to Yangzhou University, Xinhua 225700, Jiangsu Province, China;
2. Obstetrics and Gynecology Department, Xinhua People's Hospital Affiliated to Yangzhou University, Xinhua 225700, Jiangsu Province, China;
3. Pathological Department, Xinhua People's Hospital Affiliated to Yangzhou University, Xinhua 225700, Jiangsu Province, China;

Corresponding author：

YAOChun, Email: lengyue19860426@163.com

Keywords：

Colonrectal cancer; Cyclin dependent kinase 8; Transforming growth factor-β1

DOI：

10.7507/1007-9424.20160213

Video：

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Objective To investigate the expression and clinical significance of cyclin dependent kinase 8 (CDK8) and transforming growth factor-β1 (TGF-β1), and their correlation in human colorectal cancer tissues. Methods The CDK8 and TGF-β1 mRNA expressions were examined by using real-time quantitative polymerase chain reaction and the protein expresssions of them were detected by immunohistochemistry on a cohort of human colorectal cancer tissues (n=40) and corresponding adjacent tissues (n=40). The correlation between CDK8 and TGF-β1 was also analyzed. Results The expression levels of CDK8 mRNA and TGF-β1 mRNA in colorectal cancer were dramatically increased compared with the corresponding adjacent tissues (P < 0.05). The expression level of CDK8 mRNA was significantly associated with lymphnode metastasis, depth of invasion, and colorectal cancer stage (P < 0.05). However, the expression level of CDK8 mRNA was no correlation with the age, gender of patients, tumor size and differentiation of colorectal cancer in this study. The expression level of TGF-β1 mRNA was significantly associated with lymphnode metastasis, depth of invasion, tumor size and colorectal cancer stage (P < 0.05). However, the expression level of TGF-β1 mRNA was no correlation with the age, gender of patients and differentiation of colorectal cancer. The expressions of CDK8 mRNA and TGF-β1 mRNA in colorectal cancer was positively correlated (r=0.387, P=0.048). Conclusions The upregulation of CDK8 and TGF-β1 expression may be related to the occurrence and development of colorectal cancer, and the two may have a synergistic effect, which may be related to the biological behavior and prognosis of colorectal cancer.

Citation： WUDuo, XUDa-fang, ZHAOQun, YAOChun, ZHANGXiu-mei. Expressions of mRNA and Protein of CDK8 and TGF-β1 in Colorectal Cancer and Its Relation to Clinicopathological Features. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(7): 813-817. doi: 10.7507/1007-9424.20160213 Copy

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3.	李贞, 孙小丽, 吴坤河, 等. CDK8在宫颈癌及宫颈上皮内瘤变中表达及意义的初步研究.实用妇产科杂志, 2013, 29(11): 848-852.
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6.	朱亚青, 陈澍周, 陈玉泉, 等. TGF-β1和TβRⅠ在胆囊癌发病及预后中的作用.中国普外基础与临床杂志, 2007, 14(4): 448-452.
7.	Kim S, Lee J, Jeon M, et al. Elevated TGF-β1 and-β2 expression accelerates the epithelial to mesenchymal transition in triple-negative breast cancer cells. Cytokine, 2015, 75(1): 151-158.
8.	Li XY, Luo QF, Wei CK, et al. siRNA-mediated silencing of CDK8 inhibits proliferation and growth in breast cancer cells, Int J Clin Exp Pathol, 2013, 7(1): 92-100.
9.	Ko H. Geraniin inhibits TGF-β1-induced epithelial–mesenchymal transition and suppresses A549 lung cancer migration, invasion and anoikis resistance. Bioorg Med Chem Lett, 2015, 25(17): 3529-3534.
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12.	Alarcón C, Zaromytidou AI, Xi Q, et al. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta path-ways. Cell, 2009, 139(4): 757-769.
13.	Sebio A, Kahn M, Lenz HJ. The potential of targeting wnt/β-catenin in colon cancer. Exp Opin Ther Targets, 2014, 18(6): 611-615.
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15.	Fan K, Li N, Qi JJ, et al. Wnt/β-catenin signaling induces the tran-scription of cystathionine-γ-lyase, a stimulator of tumor in colon cancer. Cellular Signalling, 2014, 26(12): 2801-2808.
16.	Zhao J, Ramos R, Demma M. CDK8 regulates E2F1 transcriptional activity through S375 phosphorylation. Oncogene, 2013, 32(30): 3520-3530.
17.	Firestein R, Shima K, Nosho K, et al. CDK8 expression in 470 colore-ctal cancers in relation to beta-catenin activation, other molecular alterations and patient survival. Int J Cancer, 2010, 126(12): 2863-2873.
18.	Cai WS, Shen F, Feng Z, et al. Downregulation of CDK-8 inhibits colon cancer hepatic metastasis by regulating Wnt/β-catenin pathway. Biomed Pharmacother, 2015, 74: 153-157.
19.	Gu W, Wang W, Li W, et al. Tumor-suppressive effects of CDK8 in endometrial cancer cells. Cell Cycle, 2013, 12(6): 987-999.
20.	Wendt MK, Tian M, Schiemann WP. Deconstructing the mechanisms and consequences of TGF-β-induced EMT during cancer progre-ssion. Cell Tissue Res, 2012, 347(1): 85-101．.
21.	Farid IM, Hamza IM, El-Abd DM, et al. Transforming growth factor-β1 gene expression in hepatocellular carcinoma: a preliminary report. Arab J Gastroenterol, 2014, 15(3-4): 142-147．.
22.	Nakamura S, Yaguchi T, Kawamura N, et al. TGF-β1 in tumor micro-environments induces immunosuppression in the tumors and sentinel lymph nodes and promotes tumor progression. J Immunother, 2014, 37(2): 63-72.
23.	Li JP, Liu H, Yu JP. Chemoresistance to doxorubicin induces epithelial-mesenchymal transition via upregulation of transforming growth factorβsignaling in HCT116 colon cancer cells. Mol Med Rep, 2015, 12(1): 192-198.
24.	Sulkowska M, Wincewicz A, Sulkowski S, et al. Relations of TGF-b1 with HIF-1a, GLUT-1 and longer survival of colorectal cancer patients. Pathology, 2009, 41(3): 254-260.
25.	Wang Y, Yang HY, Li L, et al. An updated meta-analysis on the association of TGF-b1 gene promoter-509C/T polymorphism with colorectal cancer risk. Cytokine, 2013, 61(1): 181-187.
26.	Koelink PJ, Hawinkels LJ, Wiercinska E, et al. 5-Aminosalicylic acid inhibits TGF-β1 signalling in colorectal cancer cells. Cytokine, 2010, 287(1): 82-90.

1. Torre LA, Bray F, Siegel RL, et al. Global Cancer Statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
2. Chen WQ, Zheng RS, Zuo TT, et al. National cancer incidence and mortality in China, 2012. Chin J Cancer Res, 2016, 28(1): 1-11.
3. 李贞, 孙小丽, 吴坤河, 等. CDK8在宫颈癌及宫颈上皮内瘤变中表达及意义的初步研究.实用妇产科杂志, 2013, 29(11): 848-852.
4. 李津, 钟美佐.β-catenin、ＲIPK4、CDK8在套细胞淋巴瘤中的表达及临床意义.临床肿瘤学杂志, 2015, 20(3): 233-237.
5. Kim MY, Han SI, Lim SC. Roles of cyclin-dependent kinase 8 andβ-catenin in the oncogenesis and progression of gastric adenocarci-noma. Int J Oncol, 2011, 38(5) : 1375-1383.
6. 朱亚青, 陈澍周, 陈玉泉, 等. TGF-β1和TβRⅠ在胆囊癌发病及预后中的作用.中国普外基础与临床杂志, 2007, 14(4): 448-452.
7. Kim S, Lee J, Jeon M, et al. Elevated TGF-β1 and-β2 expression accelerates the epithelial to mesenchymal transition in triple-negative breast cancer cells. Cytokine, 2015, 75(1): 151-158.
8. Li XY, Luo QF, Wei CK, et al. siRNA-mediated silencing of CDK8 inhibits proliferation and growth in breast cancer cells, Int J Clin Exp Pathol, 2013, 7(1): 92-100.
9. Ko H. Geraniin inhibits TGF-β1-induced epithelial–mesenchymal transition and suppresses A549 lung cancer migration, invasion and anoikis resistance. Bioorg Med Chem Lett, 2015, 25(17): 3529-3534.
10. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2^-ΔCt Method. Methods, 2001, 30(4): 402-408.
11. Firestein R, Bass AJ, Kim SY, et al. CDK8 is a colorectal cancer onco-gene that regulates beta-catenin activity. Nature, 2008, 455(7212): 547-551.
12. Alarcón C, Zaromytidou AI, Xi Q, et al. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta path-ways. Cell, 2009, 139(4): 757-769.
13. Sebio A, Kahn M, Lenz HJ. The potential of targeting wnt/β-catenin in colon cancer. Exp Opin Ther Targets, 2014, 18(6): 611-615.
14. Tai WP, Hu PJ, Wu J, et al. The inhibition of wnt/beta-catenin signa-ling pathway in human colon cancer cells by sulindac. Tumori, 2014, 100(1): 97-101.
15. Fan K, Li N, Qi JJ, et al. Wnt/β-catenin signaling induces the tran-scription of cystathionine-γ-lyase, a stimulator of tumor in colon cancer. Cellular Signalling, 2014, 26(12): 2801-2808.
16. Zhao J, Ramos R, Demma M. CDK8 regulates E2F1 transcriptional activity through S375 phosphorylation. Oncogene, 2013, 32(30): 3520-3530.
17. Firestein R, Shima K, Nosho K, et al. CDK8 expression in 470 colore-ctal cancers in relation to beta-catenin activation, other molecular alterations and patient survival. Int J Cancer, 2010, 126(12): 2863-2873.
18. Cai WS, Shen F, Feng Z, et al. Downregulation of CDK-8 inhibits colon cancer hepatic metastasis by regulating Wnt/β-catenin pathway. Biomed Pharmacother, 2015, 74: 153-157.
19. Gu W, Wang W, Li W, et al. Tumor-suppressive effects of CDK8 in endometrial cancer cells. Cell Cycle, 2013, 12(6): 987-999.
20. Wendt MK, Tian M, Schiemann WP. Deconstructing the mechanisms and consequences of TGF-β-induced EMT during cancer progre-ssion. Cell Tissue Res, 2012, 347(1): 85-101．.
21. Farid IM, Hamza IM, El-Abd DM, et al. Transforming growth factor-β1 gene expression in hepatocellular carcinoma: a preliminary report. Arab J Gastroenterol, 2014, 15(3-4): 142-147．.
22. Nakamura S, Yaguchi T, Kawamura N, et al. TGF-β1 in tumor micro-environments induces immunosuppression in the tumors and sentinel lymph nodes and promotes tumor progression. J Immunother, 2014, 37(2): 63-72.
23. Li JP, Liu H, Yu JP. Chemoresistance to doxorubicin induces epithelial-mesenchymal transition via upregulation of transforming growth factorβsignaling in HCT116 colon cancer cells. Mol Med Rep, 2015, 12(1): 192-198.
24. Sulkowska M, Wincewicz A, Sulkowski S, et al. Relations of TGF-b1 with HIF-1a, GLUT-1 and longer survival of colorectal cancer patients. Pathology, 2009, 41(3): 254-260.
25. Wang Y, Yang HY, Li L, et al. An updated meta-analysis on the association of TGF-b1 gene promoter-509C/T polymorphism with colorectal cancer risk. Cytokine, 2013, 61(1): 181-187.
26. Koelink PJ, Hawinkels LJ, Wiercinska E, et al. 5-Aminosalicylic acid inhibits TGF-β1 signalling in colorectal cancer cells. Cytokine, 2010, 287(1): 82-90.

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Expressions of mRNA and Protein of CDK8 and TGF-β1 in Colorectal Cancer and Its Relation to Clinicopathological Features

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