Downregulation of miR203 induces overexpression of PIK3CA and predicts poor prognosis of gastric cancer patients.
Downregulation of miR203 induces overexpression of PIK3CA and predicts poor prognosis of gastric cancer patients.
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DOI：
10.2147/dddt.s85525
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Zhou X
中科院分区：
文献类型：
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作者：
Liang M;Shi B;Liu J;He L;Yi G;Zhou L;Yu G;Zhou X
尽管临床治疗和技术不断进步，但胃癌患者的预后仍然很差。本研究的目的是探讨新的胃癌预后预测指标。在这项研究中，我们评估了PIK 3CA在107例胃癌标本及其邻近非肿瘤组织中的表达模式。合成PIK 3CA siRNA并转染胃癌细胞系。采用集落形成法和MTT法检测细胞增殖情况。免疫组化和Western blot检测PIK 3CA的表达。Transwell侵袭实验检测细胞的侵袭能力。用3′-非翻译区荧光素酶报告基因检测荧光素酶活性。我们观察到PIK 3CA在胃癌组织中显著上调。PIK 3CA在48例（44.86%）胃癌组织中呈高表达，且与预后不良相关。此外，我们的研究表明miR 203通过直接靶向和抑制PIK 3CA表达来抑制细胞增殖和侵袭。MiR 203在胃癌组织中表达下调。此外，miR 203的低表达水平预测胃癌患者的不良预后，并诱导PIK 3CA的过表达。我们的进一步研究还报道了miR 203的过表达抑制AKT的磷酸化，而PIK 3CA的共转染逆转了miR 203的作用。我们的研究表明胃癌细胞中存在miR 203-PIK 3CA-AKT信号通路。该信号通路可能在胃癌的发生发展中起重要作用。
Despite advances in clinical therapies and technologies, the prognosis for patients with gastric cancer is still poor. The aim of this study is to investigate new predictive markers for prognosis of gastric cancer. In this study, we evaluated the expression pattern of PIK3CA in 107 gastric cancer specimens and their adjacent nontumorous tissues. PIK3CA siRNA was synthesized and transfected into gastric cancer cell lines. Colony formation and MTT assays were employed to analyze the cell proliferation. PIK3CA expression was examined by using immunohistochemical analysis and Western blot assay. Transwell invasion assay was used to detect the invasion capability of the cells. Luciferase activity was examined by using 3′-untranslated region luciferase reporter assays. We observed that PIK3CA was significantly upregulated in gastric cancer tissues. High expression level of PIK3CA was detectable in 48 (44.86%) of the gastric cancer specimens, and correlated with poor prognosis. In addition, our study indicated that miR203 inhibits cell proliferation and invasion via directly targeting and suppressing the PIK3CA expression. MiR203 expression is downregulated in gastric cancer tissues. Moreover, low expression level of miR203 predicted poor prognosis of gastric patients and induced overexpression of PIK3CA. Our further study also reported that overexpression of miR203 inhibited phosphorylation of AKT, while cotransfection of PIK3CA reversed the effect of miR203. Our study suggested a miR203-PIK3CA-AKT signaling pathway in gastric cancer cells. This signaling pathway might play an important role in gastric cancer genesis and development.