The miR-18a*microRNA functions as a potential tumor suppressor by targeting on K-Ras
The miR-18a*microRNA functions as a potential tumor suppressor by targeting on K-Ras
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DOI：
10.1093/carcin/bgp094
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发表时间：
2009-06-01
期刊：
影响因子：
4.7
通讯作者：
Kwok, Tim Tak
中科院分区：
文献类型：
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作者：
Tsang, Wing Pui;Kwok, Tim Tak
Ras原癌基因介导多种细胞事件，在癌症中经常发生突变。MicroRNAs （miRNAs）可能通过对靶基因的影响来调节癌症的发展。在寻找靶向Ras的mirna中，miR-18a*首次被证实靶向K-Ras，并且不靶向N-和H-Ras。通过转染anti-miR-18a*抑制剂抑制miR-18a*，可以增加K-Ras的表达以及含有K-Ras信使RNA 3'-未翻译区的报告结构体的荧光素酶活性。此外，miR-18a*的抑制也增加了细胞的增殖，促进了人鳞癌A431细胞、结肠癌HT-29细胞和胎儿肝脏WRL-68细胞在软琼脂中的不依赖锚定生长。另一方面，通过转染miR-18a*前体异位表达miR-18a*可抑制K-Ras的表达、细胞增殖和A431细胞的非锚定生长。然而，抑制miR-18a*后细胞增殖和非锚定生长的增加是由Ras抑制剂法尼基硫代水杨酸引起的。总之，miR-18a*可能通过靶向K-Ras发挥抑癌作用。因此，miRNA也可能是癌症治疗的潜在治疗剂或靶点。
The Ras proto-oncogene mediates a wide variety of cellular events and is frequently mutated in cancer. MicroRNAs (miRNAs) may regulate the development of cancer through their effect on the target genes. In the search of miRNAs that target on Ras, miR-18a* is the first time confirmed to target on K-Ras and furthermore not on N- and H-Ras. miR-18a* repression by transfection with anti-miR-18a* inhibitor increased the K-Ras expression as well as the luciferase activity of a reporter construct containing the 3'-untranslated region of K-Ras messenger RNA. Furthermore, the miR-18a* repression also increased the cell proliferation and promoted the anchorage-independent growth in soft agar of human squamous carcinoma A431 cells, colon adenocarcinoma HT-29 cells and fetal hepatic WRL-68 cells. On the other hand, ectopic expression of miR-18a* by transfection with miR-18a* precursor suppressed K-Ras expression, cell proliferation and anchorage-independent growth of A431 cells. The increase in cell proliferation and anchorage-independent growth upon miR-18a* repression was, however, rendered by the Ras inhibitor farnesylthiosalicylic acid. In conclusion, miR-18a* may function as a tumor suppressor by targeting on K-Ras. Therefore, the miRNA may also be a potential therapeutic agent or target for cancer therapy.