Department of Cellular and Molecular Biology, Hiroshima University Graduate School of Biomedical Science, Hiroshima, Japan.
Jpn J Clin Oncol. 2013 May;43(5):579-82. doi: 10.1093/jjco/hyt037. Epub 2013 Mar 13.
The joint international symposium of the 22nd Hiroshima Cancer Seminar and the 4th Japanese Association for RNA Interference focused on a pivotal role of microRNAs in carcinogenesis, progression and therapy of human cancer. Mammalian immune regulator MCPIP1 (Zc3h12a) RNase acts as a novel suppressor of microRNA activity and biogenesis, suggesting the involvement of MCPIP1 in the alteration of microRNA biogenesis in tumorigenesis. Gene set enrichment analysis and functional assignment of microRNAs via enrichment analysis enable the prediction of microRNA activities from mRNA expression data by combining rank-based enrichment analysis and weighted evaluation of microRNA-mRNA interactions. MiR-124 and miR-203 function as tumor-suppressor microRNAs silenced by DNA methylation in hepatocellular carcinoma. Stella-induced DNA hypomethylation would confer the pathogenic function of DNA hypomethylation in cancer. Senescence-associated microRNA, miR-22, suppresses tumor growth and metastasis in vivo in a murine breast cancer model, and exosomal senescence-associated microRNA may affect the tumor microenvironment. The therapeutic potential of microRNAs for preventing and treating lung cancer using the Kras(LSL-G12D/+);p53(LSL-R172H/+)mouse model suggests that miR-34 may be useful in sensitizing tumors to other conventional therapeutics. MiR-1 and miR-133a cluster may function as tumor suppressors regulating novel pathways in human cancers. The down-regulation of miR-148a is implicated in invasion of gastric cancer, while high miR-21 expression in colorectal cancer is associated with poor survival. Neutral sphingomyelinase 2 regulates exosomal microRNA secretion and promotes angiogenesis within the tumor microenvironment as well as metastasis; in particular, the exosomal miR-210 secretion by neutral sphingomyelinase 2 confers the formation of the tumor vessel network.
第 22 届广岛癌症研讨会和第 4 届日本 RNA 干扰协会联合国际研讨会的重点是 microRNA 在人类癌症的发生、进展和治疗中的关键作用。哺乳动物免疫调节剂 MCPIP1（Zc3h12a）RNase 作为 microRNA 活性和生物发生的新型抑制剂发挥作用，表明 MCPIP1 参与了肿瘤发生中 microRNA 生物发生的改变。通过富集分析和加权评估 microRNA-mRNA 相互作用，对 microRNA 进行基因集富集分析和功能分配，使我们能够通过结合基于秩的富集分析和加权评估 microRNA-mRNA 相互作用，从 mRNA 表达数据中预测 microRNA 活性。miR-124 和 miR-203 作为抑癌 microRNA，在肝癌中被 DNA 甲基化沉默。Stella 诱导的 DNA 低甲基化会赋予 DNA 低甲基化在癌症中的致病功能。衰老相关 microRNA，miR-22，在小鼠乳腺癌模型中体内抑制肿瘤生长和转移，外泌体衰老相关 microRNA 可能影响肿瘤微环境。Kras（LSL-G12D/+）；p53（LSL-R172H/+）小鼠模型中使用 microRNAs 预防和治疗肺癌的治疗潜力表明，miR-34 可能有助于使肿瘤对其他常规疗法敏感。miR-1 和 miR-133a 簇可能作为肿瘤抑制因子，在人类癌症中调节新的途径。miR-148a 的下调与胃癌的侵袭有关，而结直肠癌中高表达的 miR-21 与不良预后相关。中性鞘磷脂酶 2 调节外泌体 microRNA 的分泌，并促进肿瘤微环境中的血管生成和转移；特别是，中性鞘磷脂酶 2 分泌的外泌体 miR-210 赋予了肿瘤血管网络的形成。
