miR-422a inhibits cell proliferation in colorectal cancer by targeting AKT1 and MAPK1.
miR-422a inhibits cell proliferation in colorectal cancer by targeting AKT1 and MAPK1.
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miR-422a 通过靶向 AKT1 和 MAPK1 抑制结直肠癌细胞增殖
DOI：
10.1186/s12935-017-0461-3
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发表时间：
2017
影响因子：
5.8
通讯作者：
Liao WT
中科院分区：
文献类型：
--
作者：
Wei WT;Nian XX;Wang SY;Jiao HL;Wang YX;Xiao ZY;Yang RW;Ding YQ;Ye YP;Liao WT
研究背景miRNAs被认为是结直肠癌（colorectal cancer，CRC）的分子生物学标志物和治疗靶点，一系列miRNAs已被证实参与了CRC的发生、侵袭和转移。miR-422 a的异常表达及其作用在某些癌症中已有报道。然而，miR-422 a在结直肠癌发生发展中的作用及其机制尚不清楚。体内和体外功能测定均显示miR-422 a抑制CRC细胞增殖。进行靶标预测程序（miRBase）和荧光素酶报告基因测定以确认miR-422 a的靶基因AKT 1和MAPK 1。采用实时荧光定量PCR方法检测50例结直肠癌组织中miR-422 a的表达，并分析miR-422 a与靶基因AKT 1和MAPK 1表达的相关性。miR-422 a的异位表达抑制了细胞增殖和肿瘤生长能力;相反，内源性miR-422 a的抑制促进了CRC细胞的细胞增殖和肿瘤生长能力。miR-422 a直接作用于AKT 1和MAPK 1的3′-UTR，下调miR-422 a可激活Raf/MEK/ERK和PI 3 K/AKT信号通路，促进结直肠癌细胞增殖。结论miR-422 a通过靶向AKT 1和MAPK 1抑制结直肠癌细胞增殖。
BackgroundmiRNAs are regarded as molecular biomarkers and therapeutic targets for colorectal cancer (CRC), a series of miRNAs have been proven to involve into CRC carcinogenesis, invasion and metastasis. Aberrant miR-422a expression and its roles have been reported in some cancers. However, the function and underlying mechanism of miR-422a in the progression of CRC remain largely unknown.MethodsReal-time PCR were used to quantify miR-422a expression in CRC tissues. Both vivo and vitro functional assays showed miR-422a inhibits CRC cell proliferation. Target prediction program (miRBase) and luciferase reporter assays were conducted to confirm the target genes AKT1 and MAPK1 of miR-422a. Specimens from 50 patients with CRC were analyzed for the correlation between the expression of miR-422a and the expression of the target genes AKT1 and MAPK1 by real-time PCR.ResultsMiR-422a was down‑regulated in CRC tissues and cell lines. Ectopic expression of miR-422a inhibited cell proliferation and tumor growth ability; inhibition of endogenous miR-422a, by contrast, promoted cell proliferation and tumor growth ability of CRC cells. MiR-422a directly targets 3′-UTR of the AKT1 and MAPK1, down-regulation of miR-422a led to the activation of Raf/MEK/ERK and PI3K/AKT signaling pathways to promote cell proliferation in CRC. In addition, miR-422a expression was negatively correlated with the expressions of AKT1 and MAPK1 in CRC tissues.ConclusionmiR-422a inhibits cell proliferation in colorectal cancer by targeting AKT1 and MAPK1.
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