Differential Expressions of Seven MicroRNAs Between Primary Hepatocellular Carcinoma and Adjacent Nontumorous Tissues and Their Correlations with Levels of Tumor Markers in Serum_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Ming , LIU Weihui , YOU Nan , ZHANG Fuqin , DOU Kefeng

Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, China;

Corresponding author：

Keywords：

MicroRNAs; MiR-200a; Primary hepatocellular carcinoma; Alpha fetal protein

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Objective To explore the differential expressions of seven microRNAs between hepatocellular carcinoma (HCC) and adjacent nontumorous tissues (NT), analyze the correlations between differential expressing microRNAs and the levels of tumor markers in serum, and furnish evidence for novel diagnostic and prognostic tool of HCC. Methods Real-time quantitative PCR technique was used to measure the differential expressions of seven microRNAs in HCC tissues compared with NT. Results Compared with NT, the relative expressions of seven microRNAs in HCC tissues manifested statistical difference (P lt;0.05). MiR-34c, miR-21, miR-16, and miR-10b presented higher expressions in the HCC samples than those in the NT samples, while miR-200a, miR-148b, and miR-Let-7i demonstrated lower expressions in the HCC samples than those in the NT samples. In addition, miR-200a and miR-148b were markedly down-regulated in the HCC tissues than those in the NT. The differential expressions of miR-200a in HCC compared with NT samples was correlated with serum AFP level of the patients (r=0.848 9, P lt;0.01), while the differential expressions of the other six microRNAs had no correlation with the levels of tumor markers in serum (P gt;0.05). Conclusions There are differential expressions of microRNAs between HCC and NT. MiR-200a may serve as a novel diagnostic and prognostic tool of HCC.

Citation： ZHANG Ming,LIU Weihui,YOU Nan,ZHANG Fuqin,DOU Kefeng. Differential Expressions of Seven MicroRNAs Between Primary Hepatocellular Carcinoma and Adjacent Nontumorous Tissues and Their Correlations with Levels of Tumor Markers in Serum. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(6): 562-566. doi: Copy

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1. Kim VN, Nam JW. Genomics of microRNA [J]. Trends Genet, 2006; 22(3): 165-173.
2. Ke XS, Liu CM, Liu DP, et al. MicroRNAs: key participants in gene regulatory networks [J]. Curr Opin Chem Biol, 2003; 7(4): 516-523.
3. Dillhoff M, Wojcik SE, Bloomston M. MicroRNAs in solid tumors [J]. J Surg Res, 2009; 154(2): 349-354.
4. Osada H, Takahashi T. MicroRNAs in biological processes and carcinogenesis [J]. Carcinogenesis, 2007; 28(1): 2-12.
5. Lagos-Quintana M, Rauhut R, Lendeckel W, et al. Identification of novel genes coding for small expressed RNAs [J]. Science, 2001; 294(5543): 853-858.
6. Reinhart BJ, Weinstein EG, Rhoades MW, et al. Micro-RNAs in plants [J]. Genes Dev, 2002; 16(13): 1616-1626.
7. Ambros V. The functions of animal microRNAs [J]. Nature, 2004; 431(7006): 350-355.
8. Jin P, Alisch RS, Warren ST. RNA and microRNAs in fragile X mental retardation [J]. Nat Cell Biol, 2004; 6(11): 1048-1053.
9. Gregory RI, Yan KP, Amuthan G, et al. The Microprocessor complex mediates the genesis of microRNAs [J]. Nature, 2004; 432(7014): 235-240.
10. McGlynn KA, Tsao L, Hsing AW, et al. International trends and patterns of primary liver cancer [J]. Int J Cancer, 2001; 94(2): 290-296.
11. Murakami Y, Yasuda T, Saigo K, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues [J]. Oncogene, 2006; 25(17): 2537-2545.
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13. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers [J]. Nature, 2005; 435(7043): 834-838.
14. Horie Y, Suzuki A, Kataoka E, et al. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas [J]. J Clin Invest, 2004; 113(12): 1774-1783.
15. Meng F, Henson R, Lang M, et al. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines [J]. Gastroenterology, 2006; 130(7): 2113-2129.
16. Okamura K, Ishizuka A, Siomi H, et al. Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways [J]. Genes Dev, 2004; 18(14): 1655-1666.
17. Esquela-Kerscher A, Slack FJ. Oncomirs-microRNAs with a role in cancer [J]. Nat Rev Cancer, 2006; 6(4): 259-269.
18. Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family [J]. Cell, 2005; 120(5): 635-647.
19. O’Donnell KA, Wentzel EA, Zeller KI, et al. c-Myc-regulated microRNAs modulate E2F1 expression. [J]. Nature, 2005; 435(7043): 839-843.
20. Budhu A, Jia HL, Forgues M, et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma [J]. Hepatology, 2008; 47(3): 897-907.
21. Gregory PA, Bert AG, Paterson EL, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 [J]. Nat Cell Biol, 2008; 10(5): 593-601.
22. Taketa K. Alpha-fetoprotein: reevaluation in hepatology [J]. Hepatology, 1990; 12(6): 1420-1432.
23. 邵浙新，徐骁，郑树森，等．肝细胞癌患者肝移植术后甲胎蛋白的变化与肿瘤复发 [J]．中华普通外科杂志， 2006; 21(5)： 351-353．.
24. 劳明，朱波，黄玲莎，等．三种肿瘤标志物联合检测对原发性肝癌的诊断价值 [J]．中华消化杂志， 2005; 25(2)： 109-110．.
25. 马京香, 宫奇林, 林梅青，等．多项肿瘤标志物联合检测早期诊断原发性肝癌的研究 [J]．中华外科杂志， 2000; 38(1)： 14-16．.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Differential Expressions of Seven MicroRNAs Between Primary Hepatocellular Carcinoma and Adjacent Nontumorous Tissues and Their Correlations with Levels of Tumor Markers in Serum

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