MicroRNA-520c-3p functions as a novel tumor suppressor in lung adenocarcinoma
MicroRNA-520c-3p functions as a novel tumor suppressor in lung adenocarcinoma
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MicroRNA-520c-3p 在肺腺癌中发挥新型肿瘤抑制作用
DOI：
10.1111/febs.14835
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发表时间：
2019-07-01
期刊：
影响因子：
5.4
通讯作者：
Yu, Xiaozhou
中科院分区：
文献类型：
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作者：
Li, Xiaofeng;Fu, Qiang;Yu, Xiaozhou
肺癌是发病率最高的恶性肿瘤之一，是癌症相关死亡的主要原因。为了进一步了解肿瘤生长和转移的潜在机制，我们研究了microRNA在肺腺癌（LUAD）中的作用和表达。我们发现microRNA-520 c-3 p（miR-520 c-3 p）在LUAD组织中的表达水平显著低于非肿瘤组织。已知miR-520 c-3 p调节多种生物学功能和细胞行为。在这项研究中，我们发现AKT 1和AKT 2是miR-520 c-3 p的关键直接靶点，这是其在LUAD中的生物学作用所必需的。从机制上讲，LUAD中miR-520 c-3 p的下调是由于miR-520 c-3 p启动子区域的DNA甲基化。相反，转录因子Yin Yang 1（YY 1）的活性导致miR-520 c-3 p的上调。综上所述，我们的研究结果揭示了甲基化/YY 1/miR-520 c-3 p/AKT 1/AKT 2作为具有有效生物学功能的分子轴，并突出了miR-520 c-3 p作为LUAD中新的有效肿瘤抑制因子。
Lung cancer is a malignancy with one of the highest incidence rates, and it is the leading cause of cancer-related death. To gain further insights into the underlying mechanisms of tumor growth and metastasis, we investigated the role and expression of microRNAs in lung adenocarcinoma (LUAD). We discovered a significantly lower expression level of microRNA-520c-3p (miR-520c-3p) in LUAD tissues than in nontumor tissues. miR-520c-3p is known to regulate multiple biological functions and cellular behaviors. In this study, we show that AKT1 and AKT2 are key direct targets of miR-520c-3p, which are required for its biological roles in LUAD. Mechanistically, downregulation of miR-520c-3p in LUAD is due to DNA methylation of the miR-520c-3p promoter region. Conversely, the activity of the transcription factor Yin Yang 1 (YY1) results in the upregulation of miR-520c-3p. Taken together, our results reveal methylation/YY1/miR-520c-3p/AKT1/AKT2 as a molecular axis with a potent biological function and highlight miR-520c-3p as a novel potent tumor suppressor in LUAD.