miRNA-302-367 簇通过 novel target AKT1 抑制宫颈癌细胞的增殖。
The microRNA-302-367 cluster suppresses the proliferation of cervical carcinoma cells through the novel target AKT1.
机构信息
Department of Reproductive Medicine, First Affiliated Hospital, Xi'an Jiaotong UniversityMedical School, Xi'an 710061, The People's Republic of China.
出版信息
RNA. 2013 Jan;19(1):85-95. doi: 10.1261/rna.035295.112. Epub 2012 Nov 26.
Abstract
The miR-302-367 cluster is specifically expressed in human embryonic stem cells and has been shown to convert human somatic cells into induced pluripotent stem cells. Here, we investigated the role of the miR-302-367 cluster in cervical carcinoma. The cluster was not endogenously expressed in cervical cancer cells, and its ectopic expression did not reprogram the cervical cancer cells to an embryonic stem cell-like state. However, ectopic expression of the miR-302-367 cluster in HeLa and SiHa cervical cancer cells inhibited cell proliferation and tumor formation by blocking the G1/S cell cycle transition. We identified a new cell cycle regulatory pathway in which the miR-302-367 cluster directly down-regulated both cyclin D1 and AKT1 and indirectly up-regulated p27(Kip1) and p21(Cip1), leading to the suppression of cervical cancer cell proliferation. Our findings suggest that the miR-302-367 cluster may be used as a therapeutic reagent for the treatment of cervical carcinoma.
摘要
miR-302-367 簇特异性表达于人类胚胎干细胞，并已被证明可将人类体细胞转化为诱导多能干细胞。在这里，我们研究了 miR-302-367 簇在宫颈癌中的作用。该簇在宫颈癌细胞中内源性表达，其异位表达并不能将宫颈癌细胞重新编程为胚胎干细胞样状态。然而，miR-302-367 簇在 HeLa 和 SiHa 宫颈癌细胞中的异位表达通过阻断 G1/S 细胞周期转换抑制细胞增殖和肿瘤形成。我们确定了一个新的细胞周期调控途径，其中 miR-302-367 簇直接下调细胞周期蛋白 D1 和 AKT1，并间接上调 p27(Kip1)和 p21(Cip1)，从而抑制宫颈癌细胞的增殖。我们的研究结果表明，miR-302-367 簇可作为治疗宫颈癌的治疗试剂。
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