microRNA(miRNA)是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控。近来研究发现miRNA具有癌基因或抑癌基因样作用,参与多种恶性肿瘤的演进。是肿瘤发生、发展过程中重要分子。目前已发现多种miRNAs在大肠癌组织及大肠癌细胞系中异常表达,一部分在癌细胞中较正常细胞表达明显下降如miR-143、miR-145、let-7、miR-34a等,一部分表达则升高如miR-3l、miR-21等。体外试验中将miR-143、miR-145的前体导入大肠癌细胞中,可观察到癌细胞生长受到抑制,且呈剂量依赖性。miRNA表达谱与大肠癌的生物学行为和临床分期相关,如Ⅳ期大肠癌miR-31的表达水平明显较Ⅱ期升高。而大肠癌细胞系中miRNA表达谱与癌组织差别较大,由细胞系中得到miRNA表达谱可能不适于用来推断临床样本的相应表达谱。目前研究比较多的miRNAs如miR-143、miR-145、miR-34a、let-7a等,均有抑制细胞生长增殖的作用,它们在癌细胞中表达下降导致细胞过度生长增殖,可能参与大肠癌的发生。一些化疗药物能明显影响大肠癌细胞中miRNA的表达水平,如阿霉素可明显上调miR-34的表达水平,人们推测miRNA可能是一些化疗药物发挥抗肿瘤作用的重要分子。综上,阐明大肠癌相关miRNA的作用机制将可能丰富大肠癌的病因学及分子病理学理论,为大肠癌诊断治疗提供新策略和思路。
MicroRNAs (miRNAs) are non-coding single-stranded RNAs of about 22 nucleotides that regulate a variety of cellular processes including proliferation, differentiation, and apoptosis. Recent studies suggest an important role for miRNAs in the initiation and progression of human malignancies. Some miRNAs may function as oncogenes or tumor suppressors. Changes in the expression of many miRNAs have been observed in colorectal tumor tissues and cell lines. Some of them are significantly downregulated, such as miR-143, miR-145, let-7, and miR-34a, and some are upregulated, such as miR-31and miR-21. Previous studies have demonstrated that transfection of miR-143 and miR-145 precursors into human colorectal cancer cell lines leads to significant growth inhibition in a dose-dependent manner. The miRNA expression profile has relevance to the biological behavior and clinical stage of colorectal cancer. It has been reported that the upregulation of miR-31 is significantly higher in stage IV colorectal carcinoma samples than in stage II colorectal carcinoma samples. There is a notable discrepancy in the expression profile between colorectal cancer cell lines and clinical samples. The miRNA expression profile in colorectal cell lines may not be suitable to infer miRNA expression in clinical samples. MiRNAs such as miR-143, miR-145, and miR-34a have the potential of inhibiting cell growth and proliferation. Downregulation of these specific miRNAs in colorectal cancer cells contributes to overgrowth and out-of-control proliferation, which may be fundamental steps for colorectal cancer initiation. Moreover, some chemotherapeutic drugs can affect the expression of colorectal cancer-related miRNAs. The expression of miR-34 in colorectal cancer cell lines is increased after Adriamycin treatment. It has been inferred that miRNAs may be involved in the mechanism of chemotherapeutic drugs. Identification of the precise functions of miRNAs will further develop the etiological and pathological theories of colorectal cancer and suggest