MiR-196 and HoxB8 Influence on The Sensitivity of Neoadjuvant Chemotherapy with Folfox4 Scheme in Colorectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 HUANGLi-yong ¹ , PANJie ² ,  LUXing-rong ¹ , CHIPan ¹

1. Department of Colorectal Surgery, Affiliated Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China;
2. Department of Emergency Surgery, Affiliated Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China;

Corresponding author：

LUXing-rong, Email: lynxlxr18@163.com.cn

Keywords：

Colorectal cancer; MiR-196; HoxB8; Chemotherapy with Folfox4 scheme; RT-PCR; Immunohistochemistry

DOI：

10.7507/1007-9424.20140007

Video：

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Objective To explore the influence of patients who accepted chemotherapy of Folfox4 scheme before operation for the expression of miR-196 and HoxB8 in colorectal cancer, and illustrating the differences between the miR-196 and HoxB8 expressions in colorectal cancer tissues and sensitivity to chemotherapy with Folfox4 scheme and its corre-lation and significance. Methods Fluorescence quantitative PCR (RT-PCR) and immunohistochemistry were used to determine the expressions of miR-196 and HoxB8 in 50 specimens of neoadjuvant chemotherapy group (chemotherapy sensitive group and chemotherapy insensitive group) and 30 specimens which received the surgery directly (no-chemo-therapy group), and analyzing the relationship and discrepancy between miR-196 and HoxB8 in these groups. Results The RT-PCR examination showed that the relative expression levels of miR-196 and HoxB8 in the neoadjuvant chemo-therapy group were lower than the no-chemotherapy group (0.646 8±0.683 9 vs.1.000 0±0.000 0, P < 0.01;0.607 6±0.418 9 vs.1.000 0±0.000 0, P < 0.01).Expression of miR-196 in the chemotherapy sensitive group was higher than the chemotherapy insensitive group (0.948 9±0.691 0 vs.0.344 7±0.536 1, P < 0.01), however, the expression of HoxB8 mRNA in the chemotherapy sensitive group was lower than the chemotherapy insensitive group (0.489 9±0.371 5 vs.0.725 3±0.437 5, P < 0.05).Expression positive rate of HoxB8 protein in chemotherapy sensitive group was lower than the chemotherapy insensitive group (Z=-2.396, P=0.017).The expressions of miR-196 and HoxB8 in the neoadjuvant chemotherapy group had negative relationship (r=-0.595, P < 0.01), which was also exist in the no-chemo-therapy group (r=-0.435, P < 0.01). Conclusions The neoadjuvant chemotherapy with Folfox4 scheme before oper-ation can reduce the expression levels of miR-196 and HoxB8 in colorectal cancer tisssues.The different expression levels of miR-196 and HoxB8 could influence the sensitivity of neoadjuvant chemotherapy with Folfox4 scheme in colorectal cancer.The high level expression of miR-196 could restrain the expression of HoxB8, and then increase the sensitivity of chemotherapy with Folfox4 scheme in colorectal cancer.

Citation： HUANGLi-yong, PANJie, LUXing-rong, CHIPan. MiR-196 and HoxB8 Influence on The Sensitivity of Neoadjuvant Chemotherapy with Folfox4 Scheme in Colorectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(1): 35-39. doi: 10.7507/1007-9424.20140007 Copy

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1. Jemal A, Siegel R, Xu J, et al.Cancer statistics, 2010[J].CA Cancer J Clin, 2010, 60(5):277-300.
2. 卫生部医政司, 结直肠癌诊疗规范专家工作组.结直肠癌诊疗规范(2010年版)[J].中华胃肠外科杂志, 2010, 13(11):865-875.
3. Schimanski CC, Frerichs K, Rahman F, et al.High miR-196 levels promote the oncogenic phenotype of colorectal cancer cells[J].World J Gastroenterol, 2009, 15(17):2089-2096.
4. Eisenhauer EA, Therasse P, Bogaerts J, et al.New response evaluation criteria in solid tumours:revised RECIST guideline (version 1.1)[J].Eur J Cancer, 2009, 45(2):228-247.
5. Kreisberg JI, Malik SN, Prihoda TJ, et al.Phosphorylation of akt (ser473) is an excellent predictor of poor clinical outcome in prostate cancer[J].Cancer Res, 2004, 64(15):5232-5236.
6. Feng YZ, Shiozawa T, Miyamoto T, et al.Overexpression of hedgehog signaling molecules and its involvement in the proliferation of endometrial carcinoma cells[J].Clin Cancer Res, 2007, 13(5):1389-1398.
7. Denli AM, Tops BB, Plasterk RH, et al.Processing of primary microRNAs by the microprocessor complex[J].Nature, 2004, 432(7014):231-235.
8. Bircheler JA, Kavi HH.Molecular biology.Slicing and dicing for small RNAs[J].Science, 2008, 320(5879):1023-1024.
9. Bartel DP.MicroRNAs:genomics, biogenesis, mechanism, and function[J].Cell, 2004, 116(2):281-297.
10. Stark A, Brennecke J, Bushati N, et al.Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution[J].Cell, 2005, 123(6):1133-1146.
11. Carrington JC, Ambros V.Role of microRNAs in plant and animal development[J].Science, 2003, 301(5631):336-338.
12. Akao Y, Nakagawa Y, Naoe T.let-7 microRNA functions as a potential growth suppressor in human colon cancer cells[J].Biol Pharm Bull, 2006, 29(5):903-906.
13. Hayashita Y, Osada H, Tatematsu Y, et al.A polycistronic micro-RNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation[J].Cancer Res, 2005, 65(21):9628-9632.
14. Yekta S, Shih IH, Bartel DP.MicroRNA-directed cleavage of HOXB8 mRNA[J].Science, 2004, 304(5670):594-596.
15. Mansfield JH, Harfe BD, Nissen R, et a1.MicroRNA-responsive'sensor'transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression[J].Nat Genet, 2004, 36(10):1079-1083.
16. Tanzer A, Amemiya CT, Kim CB, et al.Evolution of microRNAs located within Hox gene clusters[J].J Exp Zool B Mol Dev Evol, 2005, 304(1):75-85.
17. Chopra VS, Mishra RK. "Mir" acles in hox gene regulation[J].Bioessays, 2006, 28(5):445-448.
18. Zhao Z, Boyle TJ, Liu Z.A negative regulatory loop between microRNA and Hox gene controls posterior identities in Caenorhabditis elegans[J].PLoS Genet, 2010, 6(9):e1001089.
19. Bloomston M, Frankel WL, Petrocca F, et al.MicroRNA expr-ession patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis[J].JAMA, 2007, 297(17):1901-1908.
20. Liao YL, Hu LY, Tsai KW, et al.Transcriptional regulation of miR-196b by ETS2 in gastric cancer cells[J].Carcinogenesis, 2012, 33(4):760-769.
21. Tsai KW, Hu LY, Wu CW, et al.Epigenetic regulation of miR-196b expression in gastric cancer[J].Genes Chromosomes Cancer, 2010, 49(11):969-980.
22. 兰洪波, 潘杰, 卢星榕, 等.miR-196b mRNA和HoxB8 mRNA在结直肠癌组织中的表达及临床意义[J].中国普外基础与临床杂志, 2013, 20(4):400-405.
23. Meng F, Henson R, Lang M, et a1.Involvement of human micro-RNAs in growth and response to chemotherapy in human cholang-iocarcinoma cell lines[J].Gastroenterology, 2006, 130(7):2113-2129.
24. Kawasaki H, Taira K.MicroRNA-196 inhibits HOXB8 expression in myeloid differentiation of HL60 cells[J].Nucleic Acids Symp Ser (Oxf), 2004, 48:211-212.
25. Hornstein E, Mansfield JH, Yekta S, et al.The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development[J].Nature, 2005, 438(7068):671-674.
26. Vider BZ, Zimber A, Hirsch D, et al.Human colorectal carcinog-enesis is associated with deregulation of homeobox gene expression[J].Biochem Biophys Res Commun, 1997, 232(3):742-748.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

MiR-196 and HoxB8 Influence on The Sensitivity of Neoadjuvant Chemotherapy with Folfox4 Scheme in Colorectal Cancer

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