Downregulation of KIAA1199 by miR-486-5p suppresses tumorigenesis in lung cancer
Downregulation of KIAA1199 by miR-486-5p suppresses tumorigenesis in lung cancer
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miR-486-5p 下调 KIAA1199 可抑制肺癌的肿瘤发生
DOI：
10.1002/cam4.3210
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发表时间：
2020-06-09
期刊：
影响因子：
4
通讯作者：
Huang, Jian-an
中科院分区：
文献类型：
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作者：
Wang, Anqi;Zhu, Jianjie;Huang, Jian-an
肺癌是我国癌症患者的主要死因，其中非小细胞肺癌（NSCLC）占绝大多数。因此，确定NSCLC肿瘤发生中涉及的生物标志物和机制至关重要。我们目前的研究发现KIAA 1199在NSCLC中的表达显著增加，并且与细胞增殖、运动和不良预后密切相关。我们证明了KIAA 1199的敲低降低了体外NSCLC细胞的生长和运动性，而KIAA 1199的过表达具有相反的效果。抑制KIAA 1199显著抑制小鼠NSCLC异种移植模型中的肿瘤生长。从机制上讲，作为表皮生长因子受体（EGFR）结合蛋白，KIAA 1199促进EGFR信号传导并调节EGFR依赖性Src、Erk和Akt磷酸化，以及EGF介导的EMT途径中的下游激酶。我们证明KIAA 1199可以作为miR-486 - 5 p的直接结合靶点，并且miR-486 - 5 p过表达可以通过调节EGFR信号通路来减弱NSCLC细胞的增殖和迁移。总之，我们的研究结果将KIAA 1199定义为一种致癌蛋白，通过调节EGF介导的信号通路促进癌细胞增殖和迁移。这项研究为NSCLC肿瘤发生提供了新的见解，这可能会导致NSCLC创新治疗计划的发展。
Lung cancer is the primary cause of death among cancer patients in China, among which nonsmall cell lung cancer (NSCLC) makes up the great majority. Hence, it is imperative to identify the biomarkers and mechanisms involved in NSCLC oncogenesis. Our present research found that KIAA1199 expression was significantly increased in NSCLC and closely related to cell proliferation, motility, and poor prognosis. We demonstrated that knockdown of KIAA1199 reduced NSCLC cell growth and motility in vitro whereas overexpression of KIAA1199 had the opposite effect. Inhibition of KIAA1199 significantly suppressed tumor growth in mouse NSCLC xenograft models. Mechanistically, as an epidermal growth factor receptor (EGFR)‐binding protein, KIAA1199 promotes EGFR signaling and regulates EGFR‐dependent Src, Erk, and Akt phosphorylation, as well as downstream kinases in the EGF‐mediated EMT pathway. We demonstrated that KIAA1199 can function as a direct binding target for miR‐486‐5p and that miR‐486‐5p overexpression can attenuate proliferation and migration of NSCLC cells via regulating the EGFR signaling pathways. To conclude, our results defined KIAA1199 as an oncogenic protein that promotes cancer cell proliferation and migration by regulating EGF‐mediated signaling pathways. This study provided new insight into NSCLC oncogenesis, which could lead to the development of innovative therapeutic plans for NSCLC.