microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway.
microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway.
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DOI：
10.1186/1476-4598-13-97
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发表时间：
2014-04-29
期刊：
影响因子：
37.3
通讯作者：
Sakuragi N
中科院分区：
文献类型：
--
作者：
Mitamura T;Watari H;Wang L;Kanno H;Kitagawa M;Hassan MK;Kimura T;Tanino M;Nishihara H;Tanaka S;Sakuragi N
我们的目的是研究 MIR31 是否是人类子宫内膜癌的癌基因，并确定与恶性表型相关的靶分子。我们研究了 MIR31 过表达 HEC-50B 细胞的体外和体内生长潜力。为了鉴定MIR31的靶分子，我们进行了荧光素酶报告基因检测，并利用人子宫内膜癌组织的免疫组织化学检查了相应的下游信号通路。我们还根据术后复发风险调查了 34 例患者中 MIR31 的表达情况。 MIR31 的过表达显着促进体外贴壁依赖性生长，并显着增加体内肿瘤形成潜力。 MIR31 与 LATS2 3'-UTR 结合显着抑制 mRNA 的荧光素酶活性，从而促进 Hippo 通路中的关键分子 YAP1 易位到细胞核中。同时，YAP1的核定位增加了CCND1的转录。此外，与低风险患者（n = 7）相比，高复发风险患者（n = 27）中MIR31的表达水平显着升高（10.7倍），并且这种较高的表达与较差的生存率相关。 MIR31 通过抑制 Hippo 通路发挥子宫内膜癌癌基因的作用。 MIR31是预测子宫内膜癌复发风险和预后的潜在新分子标志物。
We aimed to investigate whether MIR31 is an oncogene in human endometrial cancer and identify the target molecules associated with the malignant phenotype. We investigated the growth potentials of MIR31-overexpressing HEC-50B cells in vitro and in vivo. In order to identify the target molecule of MIR31, a luciferase reporter assay was performed, and the corresponding downstream signaling pathway was examined using immunohistochemistry of human endometrial cancer tissues. We also investigated the MIR31 expression in 34 patients according to the postoperative risk of recurrence. The overexpression of MIR31 significantly promoted anchorage-independent growth in vitro and significantly increased the tumor forming potential in vivo. MIR31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3’-UTR and consequently promoted the translocation of YAP1, a key molecule in the Hippo pathway, into the nucleus. Meanwhile, the nuclear localization of YAP1 increased the transcription of CCND1. Furthermore, the expression levels of MIR31 were significantly increased (10.7-fold) in the patients (n = 27) with a high risk of recurrence compared to that observed in the low-risk patients (n = 7), and this higher expression correlated with a poor survival. MIR31 functions as an oncogene in endometrial cancer by repressing the Hippo pathway. MIR31 is a potential new molecular marker for predicting the risk of recurrence and prognosis of endometrial cancer.
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影响因子：
11.2
作者：
Huang YW;Liu JC;Deatherage DE;Luo J;Mutch DG;Goodfellow PJ;Miller DS;Huang TH
通讯作者：
Huang TH
影响因子：
37.3
作者：
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Sossey-Alaoui K
影响因子：
4.7
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Alder, Hansjuerg;Taccioli, Cristian;Fong, Louise Y. Y.
通讯作者：
Fong, Louise Y. Y.
影响因子：
11.2
作者：
Liu, Chung-Ji;Tsai, Meng-Miao;Chang, Kuo-Wei
通讯作者：
Chang, Kuo-Wei
影响因子：
37.3
作者：
Dong P;Kaneuchi M;Watari H;Hamada J;Sudo S;Ju J;Sakuragi N
通讯作者：
Sakuragi N