轉移是臨床上成功治療胃癌的一大障礙，大多數(shù)胃癌患者的死亡率與轉移密切相關,。近來，microRNAs通過調控多種信號通路已成為影響轉移的關鍵因子,。
近日,，刊登在Oncogene雜志上的一項研究證實在高轉移性胃癌細胞株和腫瘤轉移組織中miR-7的表達都顯著下調。上調和降低其表達的兩項實驗表明,，miR-7表達的增加能降低胃癌細胞的遷移和侵襲能力,，而miR-7表達的降低能顯著增強腫瘤細胞的遷移和侵襲能力。
在體內轉移實驗研究中,，過表達miR-7顯著抑制胃癌轉移,。此外,，胰島素樣生長因子1受體（IGF1R）基因人癌癥患者中經常發(fā)生突變或過表達，IGF1R是一個重要的細胞生長和腫瘤浸潤調節(jié)因子,，研究證實IGF1R是miR-7的直接作用靶蛋白,。
研究人員使用siRNA沉默IGF1R的表達，miR-7具有抗腫瘤轉移潛能,，而恢復IGF1R的表達會抑制胃癌細胞中miR-7的功能,。
此外，該研究還證實miR-7通過靶向作用于IGF1R抑制Snail,，進而增加E-鈣粘素的表達,，部分逆轉上皮間質轉化（EMT）。最后胃癌淋巴結轉移組織芯片數(shù)據(jù)分析發(fā)現(xiàn)胃癌中miR-7表達與IGF1R的表達呈負相關性,。這項研究揭示了miR-7對腫瘤轉移生物學行為的影響,，理解miR-7/IGF1R/Snail信號軸將有助于開發(fā)一種新的治療方法來治療胃癌轉移。
doi:10.1038/onc.2012.156
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MicroRNA-7 functions as an anti-metastatic microRNA in gastric cancer by targeting insulin-like growth factor-1 receptor.
Zhao X, Dou W, He L, Liang S, Tie J, Liu C, Li T, Lu Y, Mo P, Shi Y, Wu K, Nie Y, Fan D.
Metastasis is a major clinical obstacle in the treatment of gastric cancer (GC) and it accounts for the majority of cancer-related mortality. MicroRNAs have recently emerged as regulators of metastasis by acting on multiple signaling pathways. In this study, we found that miR-7 is significantly downregulated in highly metastatic GC cell lines and metastatic tissues. Both gain-of-function and loss-of-function experiments showed that increased miR-7 expression significantly reduced GC cell migration and invasion, whereas decreased miR-7 expression dramatically enhanced cell migration and invasion. In vivo metastasis assays also demonstrated that overexpression of miR-7 markedly inhibited GC metastasis. Moreover, the insulin-like growth factor-1 receptor (IGF1R) oncogene, which is often mutated or amplified in human cancers and functions as an important regulator of cell growth and tumor invasion, was identified as a direct target of miR-7. Silencing of IGF1R using small interefering RNA (siRNA) recapitulated the anti-metastatic function of miR-7, whereas restoring the IGF1R expression attenuated the function of miR-7 in GC cells. Furthermore, we found that suppression of Snail by miR-7, through targeting IGF1R, increased E-cadherin expression and partially reversed the epithelial-mesenchymal transition (EMT). Finally, analyses of miR-7 and IGF1R levels in human primary GC with matched lymph node metastasis tissue arrays revealed that miR-7 is inversely correlated with IGF1R expression. The present study provides insight into the specific biological behavior of miR-7 in EMT and tumor metastasis. Targeting this novel miR-7/IGF1R/Snail axis would be helpful as a therapeutic approach to block GC metastasis
