Association of microRNA-34a overexpression with proliferation is cell type-dependent
Association of microRNA-34a overexpression with proliferation is cell type-dependent
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DOI：
10.1111/j.1349-7006.2007.00619.x
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发表时间：
2007-12-01
期刊：
影响因子：
5.7
通讯作者：
Toyokuni, Shinya
中科院分区：
文献类型：
--
作者：
Dutta, Khokon Kumar;Zhong, Yi;Toyokuni, Shinya
最近Welch等报道了微小RNA（miRNA）-34 α在神经母细胞瘤细胞中作为潜在的肿瘤抑制因子发挥作用（Oncogene 26：5017-22，2007）。在这里，我们相反地表明，miRNA-34 a支持大鼠氧化应激诱导的肾癌发生中的细胞增殖，并在各种类型的人类癌症中过表达。在寻找大鼠肾癌发生过程中遗传不稳定的染色体区域时，我们发现miRNA-34家族在染色体区域过度表达，并经常发生等位基因丢失。通过原位杂交和逆转录-聚合酶链反应，大脑神经元和浦肯野细胞的一个主要类型，miRNA-34 a的表达最高，其次是各种内分泌细胞和增殖细胞，包括生发中心淋巴细胞和小鼠胚胎成纤维细胞和干细胞。相反，正常肾小管、肝细胞和心肌细胞显示微弱的表达。在3周的次氮基三乙酸铁（Fe-NTA）诱导的氧化应激后，再生的肾近端小管细胞显示高miRNA-34 a表达。所有Fe-NTA诱导的大鼠肾癌和一系列人类癌症（177例阳性病例中有151例）均显示miRNA-34 a的高表达。此外，用小干扰RNA敲低miRNA-34 a不仅显著抑制肾癌细胞的增殖，而且抑制HeLa和MCF 7细胞的增殖。这些结果表明，miRNA-34 a过表达，在癌发生过程中获得的性状，支持大多数癌症中的细胞增殖，表明癌症和神经元和/或内分泌细胞之间的细胞代谢中的意外联系，这值得进一步研究。
Recently Welch et al. reported that microRNA (miRNA)-34a functions as a potential tumor suppressor in neuroblastoma cells (Oncogene 26: 5017-22, 2007). Here, we conversely show that miRNA-34a supports cell proliferation in rat oxidative stress-induced renal carcinogenesis and is overexpressed in various types of human cancers. While searching for genetically unstable chromosomal areas in rat renal carcinogenesis, we found the miRNA-34 family reciprocally overexpressed in chromosomal areas with frequent allelic loss. By in situ hybridization and reverse transcription-polymerase chain reaction, cerebral neurons and Purkinje cells showed the highest expression of a major type, miRNA-34a, followed by a variety of endocrine cells and proliferating cells including germinal center lymphocytes and mouse embryonic fibroblasts and stem cells. In contrast, normal renal tubules, hepatocytes and myocardial cells showed faint expression. After 3 weeks of ferric nitrilotriacetate (Fe-NTA)-induced oxidative stress, regenerating renal proximal tubular cells showed high miRNA-34a expression. All of the Fe-NTA-induced rat renal carcinomas and an array of human cancers (151 positive cases of 177) showed high expression of miRNA-34a. Furthermore, knockdown of miRNA-34a with small interfering RNA significantly suppressed proliferation not only of renal carcinoma cells but also of HeLa and MCF7 cells. These results indicate that miRNA-34a overexpression, an acquired trait during carcinogenesis, supports cell proliferation in the majority of cancers suggesting an unexpected link in the cellular metabolism between cancer and neuronal and/or endocrine cells, which warrants further investigation.