microRNA-141 is involved in a nasopharyngeal carcinoma-related genes network
microRNA-141 is involved in a nasopharyngeal carcinoma-related genes network
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microRNA-141参与鼻咽癌相关基因网络。
DOI：
10.1093/carcin/bgp335
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发表时间：
2010-04-01
期刊：
影响因子：
4.7
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
--
作者：
Zhang, Liming;Deng, Tan;Li, Guiyuan
microRNA (miRNA) 是小型非编码 RNA，与包括癌症在内的多种疾病的病理学有关。在此，我们报道鼻咽癌（NPC）细胞中最重要的癌基因之一 c-MYC 被敲低或候选抑癌基因 SPLUNC1 重新表达后，miRNA 谱发生了变化。 c-MYC 敲低和 SPLUNC1 重新表达均可下调 microRNA-141 (miR-141)。与正常鼻咽上皮相比，鼻咽癌标本中 miR-141 表达上调。抑制 miR-141 可以影响鼻咽癌细胞的细胞周期、细胞凋亡、细胞生长、迁移和侵袭。我们发现 BRD3、UBAP1 和 PTEN 是 miR-141 的潜在靶标，这在荧光素酶报告基因检测和蛋白质印迹后得到了证实。我们之前的研究证实，BRD3 和 UBAP1 均参与鼻咽癌的癌变过程，而 PTEN 是许多肿瘤类型中至关重要的抑癌基因。 BRD3 参与 Rb/E2F 通路的调节。抑制 miR-141 可能会影响 Rb/E2F、JNK2 和 AKT 通路中的一些重要分子。众所周知，鼻咽癌的癌变涉及遗传和表观遗传改变事件的网络。我们提出，miR-141 和肿瘤相关基因 c-MYC、SPLUNC1、BRD3、UBAP1 和 PTEN 可能构成基因-miRNA 网络，有助于鼻咽癌的发展。
microRNAs (miRNAs) are small non-coding RNAs and have been implicated in the pathology of various diseases, including cancer. Here we report that the miRNA profiles have been changed after knockdown of one of the most important oncogene c-MYC or re-expression of a candidate tumor suppressor gene SPLUNC1 in nasopharyngeal carcinoma (NPC) cells. Both c-MYC knockdown and SPLUNC1 re-expression can down-regulate microRNA-141 (miR-141). miR-141 is up-regulated in NPC specimens in comparison with normal nasopharyngeal epithelium. Inhibition of miR-141 could affect cell cycle, apoptosis, cell growth, migration and invasion in NPC cells. We found that BRD3, UBAP1 and PTEN are potential targets of miR-141, which had been confirmed following luciferase reporter assays and western blotting. BRD3 and UBAP1 are both involved in NPC carcinogenesis as confirmed through our previous studies and PTEN is a crucial tumor suppressor in many tumor types. BRD3 is involved in the regulation of the Rb/E2F pathway. Inhibition of miR-141 could affect some important molecules in the Rb/E2F, JNK2 and AKT pathways. It is well known that carcinogenesis of NPC is involved in the networks of genetic and epigenetic alteration events. We propose that miR-141- and tumor-related genes c-MYC, SPLUNC1, BRD3, UBAP1 and PTEN may constitute a gene-miRNA network to contribute to NPC development.