• 首都醫(yī)科大學(xué)附屬?gòu)?fù)興醫(yī)院普外科(北京 100038);

目的  研究結(jié)直腸癌肝臟轉(zhuǎn)移微小RNA (microRNA,miRNA)表達(dá)的差異以及相關(guān)特性。
方法  收集2009年4月至2010年11月期間首都醫(yī)科大學(xué)附屬?gòu)?fù)興醫(yī)院的10例伴或不伴肝臟轉(zhuǎn)移的結(jié)直腸癌患者的腫
瘤組織標(biāo)本,應(yīng)用miRNA芯片方法對(duì)2組樣本的miRNA表達(dá)差異情況進(jìn)行研究,并通過實(shí)時(shí)定量PCR對(duì)miRNA
的芯片表達(dá)差異進(jìn)行驗(yàn)證。
結(jié)果  芯片結(jié)果篩選出6種結(jié)直腸癌肝臟轉(zhuǎn)移組較非轉(zhuǎn)移組表達(dá)失調(diào)的miRNA (上調(diào)的miR-224、miR-1236和miR-622,下調(diào)的miR-155、miR-342-5p和miR-363),選取顯著上調(diào)(即差異信號(hào)值大于500)的miR-224進(jìn)行實(shí)時(shí)定量PCR驗(yàn)證,結(jié)果與芯片實(shí)驗(yàn)結(jié)果相一致。
結(jié)論  miR-224可能通過調(diào)節(jié)其靶基因而在結(jié)直腸癌肝臟轉(zhuǎn)移中起重要作用,miR-224可能成為未來結(jié)直腸癌生物標(biāo)記或治療方法的一個(gè)研究方向。

引用本文: 季曉昕,楊鋆,于德明,駱成玉. 結(jié)直腸癌肝臟轉(zhuǎn)移相關(guān)微小RNA224的研究△. 中國(guó)普外基礎(chǔ)與臨床雜志, 2013, 20(5): 499-502. doi: 復(fù)制

1. Manfredi S, Lepage C, Hatem C, et al. Epidemiology and management of liver metastases from colorectal cancer[J]. Ann Surg, 2006, 244(2):254-259.
2. Bolstad BM, Irizarry RA, Astrand M, et al. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias[J]. Bioinformatics, 2003, 19(2):185-193.
3. Livak KJ, Schmittgen TD. Analysis of relative gene expre-ssion data using real-time quantitative PCR and the 2-ΔΔCT method[J]. Methods, 2001, 25(4):402-408.
4. Cho WC. OncomiRs:the discovery and progress of microRNAs in cancers[J]. Mol Cancer, 2007, 6:60.
5. Gregory PA, Bert AG, Paterson EL, et al. The miR-200 familyand miR-205 regulate epithelial to mesenchymal transition by targe-ting ZEB1 and SIP1[J]. Nat Cell Biol, 2008, 10(5):593-601.
6. Zhang YJ, He XJ, Liu YL, et al. microRNA-320a inhibits tumor invasion by targeting neuropilin 1 and is associated with liver metas-tasis in colorectal cancer[J]. Oncol Rep, 2012, 27(3):685-694.
7. Yan LX, Huang XX, Shao Q, et al. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinicalstage, lymph node metastasis and patient poor prognosis[J]. RNA, 2008, 14(11):2348-2360.
8. Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer[J]. Oncogene, 2008, 27(15):2128-2136.
9. Wellner U, Schubert J, Burk UC, et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs[J]. Nat Cell Biol, 2009, 11(12):1487-1495.
10. 張璐. 在結(jié)腸腺癌中MicroRNA的表達(dá)方式與其預(yù)后和治療效果的相關(guān)性[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008, 15(9):698.
11. 張明, 劉衛(wèi)輝, 尤楠, 等. 7種microRNAs在原發(fā)性肝癌組織和癌旁組織間的差異表達(dá)及與血清腫瘤標(biāo)志物水平的相關(guān)性研究[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(6):562-566.
12. 顏登國(guó), 王國(guó)棟, 程海玉. 基因芯片技術(shù)分析結(jié)直腸癌肝轉(zhuǎn)移患者免疫基因表達(dá)的變化[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2012, 19(11):1182-1186.
13. Feng B, Dong TT, Wang LL, et al. Colorectal cancer migration and invasion initiated by microRNA-106a[J]. PLoS One, 2012, 7(8):e43452.
14. Hogan NM, Joyce MR, Kerin MJ. MicroRNA expression in colorectal cancer[J]. Cancer Biomark, 2012, 11(6):239-243.
15. Tokarz P, Blasiak J. The role of microRNA in metastatic colorectal cancer and its significance in cancer prognosis and treatment[J]. Acta Biochim Pol, 2012, 59(4):467-474.
16. Dong Y, Wu WK, Wu CW, et al. MicroRNA dysregulation in colorectal cancer:a clinical perspective[J]. Br J Cancer, 2011, 104(6):893-898.
17. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer[J]. Nature,.
18. Nikiforova MN, Tseng GC, Steward D, et al. MicroRNA expre-ssion profiling of thyroid tumors:biological significance and diagnostic utility[J]. J Clin Endocrinol Metab, 2008, 93(5):1600-1608.
19. Wang Yu, Lee AT, Ma JZ, et al. Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regul-ation and apoptosis inhibitor-5 as a microRNA-224-specific target[J]. J Biol Chem, 2008, 283(19):13205-13215.
20. Prueitt RL, YI M, Hudson RS, et al. Expression of microRNAs and protein-coding genes associated with perineural invasion in prostate cancer[J]. Prostate, 2008, 68(11):1152-1164.
21. Mees ST, Mardin WA, Sielker S, et al. Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas[J]. Ann Surg Oncol, 2009, 16(8):2339-2350.
22. Hildebrand J, Rütze M, Walz N, et al. A comprehensive analysis of microRNA expression during human keratinocyte differentiationin vitro and in vivo[J]. J Invest Dermatol, 2011, 131(1):20-29.
23. Bandrés E, Cubedo E, Agirre X, et al. Identification by real-timePCR of 13 mature microRNAs differentially expressed in colorectalcancer and non-tumoral tissues[J]. Mol Cancer, 2006, 5:29.
24. Schetter AJ, Leung SY, Sohn JJ, et al. MicroRNA expressionprofiles associated with prognosis and therapeutic outcome in colonadenocarcinoma[J]. JAMA, 2008, 299(4):425-436.
25. Chiang Y, Song YX, Wang ZN, et al. microRNA-192, -194 and -215 are frequently downregulated in colorectal cancer[J]. Exp Ther Med, 2012, 3(3):560-566.
26. Fu JH, Tang WT, Du P, et al. Identifying microRNA-mRNA regulatory network in colorectal cancer by a combination of expre-ssion profile and bioinformatics analysis[J]. BMC Systems Bio-logy, 2012, 6:68.
27. Mazeh H, Mizrahi I, Ilyayev N, et al. The diagnostic and prognostic role of microRNA in colorectal cancer―a comprehensive review[J]. J Cancer, 2013, 4(3):281-295.
28. , 449(7163):682-688.
  1. 1. Manfredi S, Lepage C, Hatem C, et al. Epidemiology and management of liver metastases from colorectal cancer[J]. Ann Surg, 2006, 244(2):254-259.
  2. 2. Bolstad BM, Irizarry RA, Astrand M, et al. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias[J]. Bioinformatics, 2003, 19(2):185-193.
  3. 3. Livak KJ, Schmittgen TD. Analysis of relative gene expre-ssion data using real-time quantitative PCR and the 2-ΔΔCT method[J]. Methods, 2001, 25(4):402-408.
  4. 4. Cho WC. OncomiRs:the discovery and progress of microRNAs in cancers[J]. Mol Cancer, 2007, 6:60.
  5. 5. Gregory PA, Bert AG, Paterson EL, et al. The miR-200 familyand miR-205 regulate epithelial to mesenchymal transition by targe-ting ZEB1 and SIP1[J]. Nat Cell Biol, 2008, 10(5):593-601.
  6. 6. Zhang YJ, He XJ, Liu YL, et al. microRNA-320a inhibits tumor invasion by targeting neuropilin 1 and is associated with liver metas-tasis in colorectal cancer[J]. Oncol Rep, 2012, 27(3):685-694.
  7. 7. Yan LX, Huang XX, Shao Q, et al. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinicalstage, lymph node metastasis and patient poor prognosis[J]. RNA, 2008, 14(11):2348-2360.
  8. 8. Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer[J]. Oncogene, 2008, 27(15):2128-2136.
  9. 9. Wellner U, Schubert J, Burk UC, et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs[J]. Nat Cell Biol, 2009, 11(12):1487-1495.
  10. 10. 張璐. 在結(jié)腸腺癌中MicroRNA的表達(dá)方式與其預(yù)后和治療效果的相關(guān)性[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008, 15(9):698.
  11. 11. 張明, 劉衛(wèi)輝, 尤楠, 等. 7種microRNAs在原發(fā)性肝癌組織和癌旁組織間的差異表達(dá)及與血清腫瘤標(biāo)志物水平的相關(guān)性研究[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(6):562-566.
  12. 12. 顏登國(guó), 王國(guó)棟, 程海玉. 基因芯片技術(shù)分析結(jié)直腸癌肝轉(zhuǎn)移患者免疫基因表達(dá)的變化[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2012, 19(11):1182-1186.
  13. 13. Feng B, Dong TT, Wang LL, et al. Colorectal cancer migration and invasion initiated by microRNA-106a[J]. PLoS One, 2012, 7(8):e43452.
  14. 14. Hogan NM, Joyce MR, Kerin MJ. MicroRNA expression in colorectal cancer[J]. Cancer Biomark, 2012, 11(6):239-243.
  15. 15. Tokarz P, Blasiak J. The role of microRNA in metastatic colorectal cancer and its significance in cancer prognosis and treatment[J]. Acta Biochim Pol, 2012, 59(4):467-474.
  16. 16. Dong Y, Wu WK, Wu CW, et al. MicroRNA dysregulation in colorectal cancer:a clinical perspective[J]. Br J Cancer, 2011, 104(6):893-898.
  17. 17. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer[J]. Nature,.
  18. 18. Nikiforova MN, Tseng GC, Steward D, et al. MicroRNA expre-ssion profiling of thyroid tumors:biological significance and diagnostic utility[J]. J Clin Endocrinol Metab, 2008, 93(5):1600-1608.
  19. 19. Wang Yu, Lee AT, Ma JZ, et al. Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regul-ation and apoptosis inhibitor-5 as a microRNA-224-specific target[J]. J Biol Chem, 2008, 283(19):13205-13215.
  20. 20. Prueitt RL, YI M, Hudson RS, et al. Expression of microRNAs and protein-coding genes associated with perineural invasion in prostate cancer[J]. Prostate, 2008, 68(11):1152-1164.
  21. 21. Mees ST, Mardin WA, Sielker S, et al. Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas[J]. Ann Surg Oncol, 2009, 16(8):2339-2350.
  22. 22. Hildebrand J, Rütze M, Walz N, et al. A comprehensive analysis of microRNA expression during human keratinocyte differentiationin vitro and in vivo[J]. J Invest Dermatol, 2011, 131(1):20-29.
  23. 23. Bandrés E, Cubedo E, Agirre X, et al. Identification by real-timePCR of 13 mature microRNAs differentially expressed in colorectalcancer and non-tumoral tissues[J]. Mol Cancer, 2006, 5:29.
  24. 24. Schetter AJ, Leung SY, Sohn JJ, et al. MicroRNA expressionprofiles associated with prognosis and therapeutic outcome in colonadenocarcinoma[J]. JAMA, 2008, 299(4):425-436.
  25. 25. Chiang Y, Song YX, Wang ZN, et al. microRNA-192, -194 and -215 are frequently downregulated in colorectal cancer[J]. Exp Ther Med, 2012, 3(3):560-566.
  26. 26. Fu JH, Tang WT, Du P, et al. Identifying microRNA-mRNA regulatory network in colorectal cancer by a combination of expre-ssion profile and bioinformatics analysis[J]. BMC Systems Bio-logy, 2012, 6:68.
  27. 27. Mazeh H, Mizrahi I, Ilyayev N, et al. The diagnostic and prognostic role of microRNA in colorectal cancer―a comprehensive review[J]. J Cancer, 2013, 4(3):281-295.
  28. 28. , 449(7163):682-688.
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