microRNA-141 参与鼻咽癌相关基因网络。

microRNA-141 is involved in a nasopharyngeal carcinoma-related genes network.

机构信息

Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.

出版信息

Carcinogenesis. 2010 Apr;31(4):559-66. doi: 10.1093/carcin/bgp335. Epub 2010 Jan 6.

Abstract

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.

摘要

微小 RNA(miRNAs)是小的非编码 RNA,已被牵涉到多种疾病的病理学中,包括癌症。在这里,我们报告说,在敲低最重要的癌基因 c-MYC 或重新表达候选肿瘤抑制基因 SPLUNC1 后,鼻咽癌(NPC)细胞中的 miRNA 谱发生了改变。c-MYC 敲低和 SPLUNC1 再表达均可下调 microRNA-141(miR-141)。与正常鼻咽上皮相比,NPC 标本中 miR-141 上调。抑制 miR-141 可影响 NPC 细胞的细胞周期、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,这已通过荧光素酶报告基因检测和 Western blot 得到证实。BRD3 和 UBAP1 均参与 NPC 的发生,这是我们之前的研究证实的,而 PTEN 是许多肿瘤类型中的关键肿瘤抑制因子。BRD3 参与 Rb/E2F 通路的调节。抑制 miR-141 可影响 Rb/E2F、JNK2 和 AKT 通路中的一些重要分子。众所周知,NPC 的致癌作用涉及遗传和表观遗传改变事件的网络。我们提出 miR-141 及其肿瘤相关基因 c-MYC、SPLUNC1、BRD3、UBAP1 和 PTEN 可能构成一个基因-miRNA 网络,有助于 NPC 的发展。

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