MKRN2 inhibits migration and invasion of non-small-cell lung cancer by negatively regulating the PI3K/Akt pathway.
MKRN2 inhibits migration and invasion of non-small-cell lung cancer by negatively regulating the PI3K/Akt pathway.
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DOI：
10.1186/s13046-018-0855-7
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发表时间：
2018-08-13
期刊：
影响因子：
--
通讯作者：
Qiu X
中科院分区：
文献类型：
--
作者：
Jiang J;Xu Y;Ren H;Wudu M;Wang Q;Song X;Su H;Jiang X;Jiang L;Qiu X
Makorin RING锌指-2 （MKRN2）属于Makorin RING锌指家族，是一种新的泛素E3连接酶，靶向NF-κB的p65亚基，负性调节炎症反应；然而，MKRN2与肿瘤发生之间的关系尚不清楚。在这项研究中，我们阐明了MKRN2在非小细胞肺癌（NSCLC）中的作用。从中国医科大学第一附属医院病理档案中检索2013 - 2017年261例非小细胞肺癌患者的肿瘤标本，检测MKRN2的表达，并确定MKRN2沉默和过表达对非小细胞肺癌细胞迁移和侵袭的影响。我们证明MKRN2表达与淋巴结转移、p-TNM分期、癌细胞分化和不良预后相关。通过改变选定细胞系中MKRN2的表达，我们发现MKRN2通过下调PI3K/Akt通路抑制细胞迁移和侵袭。这些结果表明，MKRN2通过降低癌细胞的转移潜能来抑制NSCLC的进展。我们的研究结果为MKRN2表达与NSCLC患者有利的临床病理特征之间的关系提供了重要的见解，并表明MKRN2在抑制NSCLC发展中起作用。
Makorin RING zinc finger-2 (MKRN2) belongs to the makorin RING zinc finger family and is a novel ubiquitin E3 ligase targeting the p65 subunit of NF-κB to negatively regulate inflammatory responses; however, the relationship between MKRN2 and tumorigenesis remains unclear. In this study, we clarified the role of MKRN2 in non-small cell lung cancer (NSCLC). Tumor specimens collected from 261 NSCLC patients from 2013 to 2017 were retrieved from the Pathology Archive of the First Affiliated Hospital of China Medical University, and we performed assays to evaluate MKRN2 expression and to determine the impact of MKRN2 silencing and overexpression on NSCLC-cell migration and invasion. We demonstrated that MKRN2 expression was associated with lymph node metastasis, p-TNM stage, cancer-cell differentiation, and poor prognosis. By altering the expression of MKRN2 in selected cell lines, we found that MKRN2 inhibited cell migration and invasion through downregulation of the PI3K/Akt pathway. These results suggested that MKRN2 inhibited NSCLC progression by reducing the metastatic potential of cancer cells. Our findings provide critical insight into the association of MKRN2 expression with favorable clinicopathological characteristics in NSCLC patients and suggested that MKRN2 plays a role in inhibiting NSCLC development.
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