• 1.福建醫(yī)科大學(xué)附屬協(xié)和醫(yī)院結(jié)直腸外科(福建福州 350001);;
  • 2. 福建醫(yī)科大學(xué)附屬協(xié)和醫(yī)院急診外科(福建福州 350001);

目的  研究miR-196b和HoxB8在結(jié)直腸癌組織中的表達(dá)及與其臨床病理特征的關(guān)系,并探討在結(jié)直腸癌組織中miR-196b與靶基因HoxB8表達(dá)的關(guān)系。
方法  用實(shí)時(shí)熒光定量PCR技術(shù)檢測(cè)30例結(jié)直腸癌組織及對(duì)應(yīng)的正常黏膜組織中miR-196bmRNA和HoxB8 mRNA的表達(dá)量,用Western blot法檢測(cè)HoxB8蛋白的表達(dá)。
結(jié)果  miR-196bmRNA和HoxB8mRNA在結(jié)直腸癌組織中的表達(dá)量均高于其在對(duì)應(yīng)的正常黏膜組織中的表達(dá)量(P<0.05)。miR-196bmRNA的表達(dá)與結(jié)直腸癌的淋巴結(jié)轉(zhuǎn)移、腫瘤分期(Ⅰ+Ⅱ與Ⅲ+Ⅳ)及遠(yuǎn)處轉(zhuǎn)移均有關(guān)
(P<0.05),而與腫瘤部位、大小、大體類型、浸潤(rùn)深度、組織分化程度、患者的年齡及性別均無(wú)關(guān)(P>0.05); HoxB8 mRNA的表達(dá)與結(jié)直腸癌的上述臨床病理特征均無(wú)關(guān)(P>0.05)。miR-196bmRNA與HoxB8mRNA的表達(dá)存在負(fù)相關(guān)(r=-0.458,P<0.05),而與HoxB8蛋白的表達(dá)無(wú)明顯相關(guān)性(r=-0.236,P>0.05)。
結(jié)論  miR-196b mRNA及HoxB8mRNA在結(jié)直腸癌組織中均呈高表達(dá), miR-196b mRNA的高表達(dá)與結(jié)直腸癌的發(fā)生、發(fā)展及預(yù)后有關(guān)。miR-196b可能通過(guò)與靶基因HoxB8 mRNA的3′非編碼區(qū)結(jié)合抑制HoxB8 mRNA的表達(dá)。

引用本文: 蘭鴻波,潘杰,盧星榕,池畔. miR-196b mRNA和HoxB8 mRNA在結(jié)直腸癌組織中的表達(dá)及其臨床意義△. 中國(guó)普外基礎(chǔ)與臨床雜志, 2013, 20(4): 400-405. doi: 復(fù)制

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2. 衛(wèi)生部醫(yī)政司. 結(jié)直腸癌診療規(guī)范專家工作組. 結(jié)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.
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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. 1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010[J]. CA Cancer J Clin, 2010, 60(5):277-300.
  2. 2. 衛(wèi)生部醫(yī)政司. 結(jié)直腸癌診療規(guī)范專家工作組. 結(jié)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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 12. Tsai KW, Hu LY, Wu CW, et al. Epigenetic regulation of miR-196b expression in gastric cancer[J]. Genes Chromosomes Cancer,.
  13. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 25. Reinhart BJ, Weinstein EG, Rhoades MW, et al. MicroRNAs in plants[J]. Genes Dev, 2002, 16(13):1616-1626.
  26. 26. , 49(11):969-980.
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