目的 研究miR-196b和HoxB8在結直腸癌組織中的表達及與其臨床病理特征的關系,并探討在結直腸癌組織中miR-196b與靶基因HoxB8表達的關系。
方法 用實時熒光定量PCR技術檢測30例結直腸癌組織及對應的正常黏膜組織中miR-196bmRNA和HoxB8 mRNA的表達量,用Western blot法檢測HoxB8蛋白的表達。
結果 miR-196bmRNA和HoxB8mRNA在結直腸癌組織中的表達量均高于其在對應的正常黏膜組織中的表達量(P<0.05)。miR-196bmRNA的表達與結直腸癌的淋巴結轉移、腫瘤分期(Ⅰ+Ⅱ與Ⅲ+Ⅳ)及遠處轉移均有關
(P<0.05),而與腫瘤部位、大小、大體類型、浸潤深度、組織分化程度、患者的年齡及性別均無關(P>0.05); HoxB8 mRNA的表達與結直腸癌的上述臨床病理特征均無關(P>0.05)。miR-196bmRNA與HoxB8mRNA的表達存在負相關(r=-0.458,P<0.05),而與HoxB8蛋白的表達無明顯相關性(r=-0.236,P>0.05)。
結論 miR-196b mRNA及HoxB8mRNA在結直腸癌組織中均呈高表達, miR-196b mRNA的高表達與結直腸癌的發(fā)生、發(fā)展及預后有關。miR-196b可能通過與靶基因HoxB8 mRNA的3′非編碼區(qū)結合抑制HoxB8 mRNA的表達。
引用本文: 蘭鴻波,潘杰,盧星榕,池畔. miR-196b mRNA和HoxB8 mRNA在結直腸癌組織中的表達及其臨床意義△. 中國普外基礎與臨床雜志, 2013, 20(4): 400-405. doi: 復制
版權信息: ?四川大學華西醫(yī)院華西期刊社《中國普外基礎與臨床雜志》版權所有,未經授權不得轉載、改編
1. | Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010[J]. CA Cancer J Clin, 2010, 60(5):277-300. |
2. | 衛(wèi)生部醫(yī)政司. 結直腸癌診療規(guī)范專家工作組. 結直腸癌診療規(guī)范(2010年版)[J]. 中華胃腸外科雜志, 2010, 13(11): 865-875. |
3. | March HN, Rust AG, Wright NA, et al. Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinaltumorigenesis[J]. Nat Genet, 2011, 43 (12):1202-1209. |
4. | Velho S, Haigis KM. Regulation of homeostasis and oncogenesis in the intestinal epithelium by ras[J]. Exp Cell Res, 2011, 317(19): 2732-2739. |
5. | Hatano Y, Yamada Y, Hata K, et al. Genetic ablation of a candidatetumor suppressor gene, Rest, does not promote mouse colon carcino-genesis[J]. Cancer Sci, 2011, 102(9): 1659-1664. |
6. | Braig S, Mueller DW, Rothhammer T, et al. MicroRNA miR-196a is a central regulator of HOX-B7 and BMP4 expression in malignant melanoma[J]. Cell Mol Life Sci, 2010, 67(20):3535-3548. |
7. | Li Y, Zhang M, Chen H, et al. Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis[J]. Cancer Res, 2010, 70(20):7894-7904. |
8. | Edge SB, Compton CC. The American Joint Committee on Cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM[J]. Ann Surg Oncol, 2010, 17(6):1471-1474. |
9. | Urbich C, Kuehbacher A, Dimmeler S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis[J]. Cardiovasc Res, 2008, 79(4):581-588. |
10. | Blenkiron C, Miska EA. miRNAs in cancer:approaches, aetiology,diagnostics and therapy[J]. Hum Mol Genet, 2007, 16 Spec No 1:R106-R113. |
11. | 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. |
12. | Tsai KW, Hu LY, Wu CW, et al. Epigenetic regulation of miR-196b expression in gastric cancer[J]. Genes Chromosomes Cancer,. |
13. | Guan Y, Mizoguchi M, Yoshimoto K, et al. MiRNA-196 is upregulated in glioblastoma but not in anaplastic astrocytoma and has prognostic significance[J]. Clin Cancer Res, 2010, 16(16):4289-4297. |
14. | Ma R, Yan W, Zhang G, et al. Upregulation of miR-196b confersa poor progno- sis inglioblastoma patients via inducing a proliferative phenotype[J]. PLoS One, 2012, 7(6):e38096. |
15. | Schimanski CC, Frerichs K, Rahman F, et al. High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells[J]. World J Gastroenterol, 2009, 15(17):2089-2096. |
16. | Benson AB 3rd, Bekaii-Saab T, Chan E, et al. Metastatic colon cancer, version 3.2013: featured updates to the NCCN guidelines[J]. J Natl Compr Canc Netw, 2013, 11(2): 141-152. |
17. | Yue Y, Farcas R, Thiel G, et al. De novo t (12;17) (p13.3;q21.3) translocation with a breakpoint near the 5′ end of the HOXB gene cluster in a patient with developmental delay and skeletal malformations[J]. Eur J Hum Genet, 2007, 15(5):570-577. |
18. | Rawat VP, Thoene S, Naidu VM, et al. Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depen-ding on its N-terminal domain and is closely correlated with dereg-ulated HOX gene expression in human acute myeloid leukemia[J]. Blood, 2008, 111(1):309-319. |
19. | Takahashi O, Hamada J, Abe M, et al. Dysregulated expression of HOX and ParaHOX genes in human esophageal squamous cell carcinoma[J]. Oncol Rep, 2007, 17(4):753-760. |
20. | Vider BZ, Zimber A, Hirsch D, et al. Human colorectal carcinogenesis is associated with deregulation of homeobox gene expression[J]. Biochem Biophys Res Commun, 1997, 232(3):742-748. |
21. | Vider BZ, Zimber A, Chastre E, et al. Deregulated expression of homeobox-containing genes, HOXB6, B8, C8, C9, and Cdx-1,in human colon cancer cell lines[J]. Biochem Biophys Res Commun, 2000, 272(2):513-518. |
22. | 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. |
23. | 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. |
24. | Lagos-Quintana M, Rauhut R, Lendeckel W, et al. Identificationof novel genes coding for small expressed RNAs[J]. Science, 2001, 294(5543):853-858. |
25. | Reinhart BJ, Weinstein EG, Rhoades MW, et al. MicroRNAs in plants[J]. Genes Dev, 2002, 16(13):1616-1626. |
26. | , 49(11):969-980. |
- 1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010[J]. CA Cancer J Clin, 2010, 60(5):277-300.
- 2. 衛(wèi)生部醫(yī)政司. 結直腸癌診療規(guī)范專家工作組. 結直腸癌診療規(guī)范(2010年版)[J]. 中華胃腸外科雜志, 2010, 13(11): 865-875.
- 3. March HN, Rust AG, Wright NA, et al. Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinaltumorigenesis[J]. Nat Genet, 2011, 43 (12):1202-1209.
- 4. Velho S, Haigis KM. Regulation of homeostasis and oncogenesis in the intestinal epithelium by ras[J]. Exp Cell Res, 2011, 317(19): 2732-2739.
- 5. Hatano Y, Yamada Y, Hata K, et al. Genetic ablation of a candidatetumor suppressor gene, Rest, does not promote mouse colon carcino-genesis[J]. Cancer Sci, 2011, 102(9): 1659-1664.
- 6. Braig S, Mueller DW, Rothhammer T, et al. MicroRNA miR-196a is a central regulator of HOX-B7 and BMP4 expression in malignant melanoma[J]. Cell Mol Life Sci, 2010, 67(20):3535-3548.
- 7. Li Y, Zhang M, Chen H, et al. Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis[J]. Cancer Res, 2010, 70(20):7894-7904.
- 8. Edge SB, Compton CC. The American Joint Committee on Cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM[J]. Ann Surg Oncol, 2010, 17(6):1471-1474.
- 9. Urbich C, Kuehbacher A, Dimmeler S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis[J]. Cardiovasc Res, 2008, 79(4):581-588.
- 10. Blenkiron C, Miska EA. miRNAs in cancer:approaches, aetiology,diagnostics and therapy[J]. Hum Mol Genet, 2007, 16 Spec No 1:R106-R113.
- 11. 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.
- 12. Tsai KW, Hu LY, Wu CW, et al. Epigenetic regulation of miR-196b expression in gastric cancer[J]. Genes Chromosomes Cancer,.
- 13. Guan Y, Mizoguchi M, Yoshimoto K, et al. MiRNA-196 is upregulated in glioblastoma but not in anaplastic astrocytoma and has prognostic significance[J]. Clin Cancer Res, 2010, 16(16):4289-4297.
- 14. Ma R, Yan W, Zhang G, et al. Upregulation of miR-196b confersa poor progno- sis inglioblastoma patients via inducing a proliferative phenotype[J]. PLoS One, 2012, 7(6):e38096.
- 15. Schimanski CC, Frerichs K, Rahman F, et al. High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells[J]. World J Gastroenterol, 2009, 15(17):2089-2096.
- 16. Benson AB 3rd, Bekaii-Saab T, Chan E, et al. Metastatic colon cancer, version 3.2013: featured updates to the NCCN guidelines[J]. J Natl Compr Canc Netw, 2013, 11(2): 141-152.
- 17. Yue Y, Farcas R, Thiel G, et al. De novo t (12;17) (p13.3;q21.3) translocation with a breakpoint near the 5′ end of the HOXB gene cluster in a patient with developmental delay and skeletal malformations[J]. Eur J Hum Genet, 2007, 15(5):570-577.
- 18. Rawat VP, Thoene S, Naidu VM, et al. Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depen-ding on its N-terminal domain and is closely correlated with dereg-ulated HOX gene expression in human acute myeloid leukemia[J]. Blood, 2008, 111(1):309-319.
- 19. Takahashi O, Hamada J, Abe M, et al. Dysregulated expression of HOX and ParaHOX genes in human esophageal squamous cell carcinoma[J]. Oncol Rep, 2007, 17(4):753-760.
- 20. Vider BZ, Zimber A, Hirsch D, et al. Human colorectal carcinogenesis is associated with deregulation of homeobox gene expression[J]. Biochem Biophys Res Commun, 1997, 232(3):742-748.
- 21. Vider BZ, Zimber A, Chastre E, et al. Deregulated expression of homeobox-containing genes, HOXB6, B8, C8, C9, and Cdx-1,in human colon cancer cell lines[J]. Biochem Biophys Res Commun, 2000, 272(2):513-518.
- 22. 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.
- 23. 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.
- 24. Lagos-Quintana M, Rauhut R, Lendeckel W, et al. Identificationof novel genes coding for small expressed RNAs[J]. Science, 2001, 294(5543):853-858.
- 25. Reinhart BJ, Weinstein EG, Rhoades MW, et al. MicroRNAs in plants[J]. Genes Dev, 2002, 16(13):1616-1626.
- 26. , 49(11):969-980.