MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2

作者：Liao, Wen-Ting; Ye, Ya-Ping; Zhang, Nian-Jie; Li, Ting-Ting; Wang, Shu-Yang; Cui, Yan-Mei; Qi, Lu; Wu, Ping; Jiao, Hong-Li; Xie, Yi-Jun; Zhang, Chi; Wang, Jun-Xian; Ding, Yan-Qing^*

来源：Journal of Pathology, 2014, 232(4): 415-427.

DOI：10.1002/path.4309

• GENE-MUTATIONS
• C-MYC
• EXPRESSION
• AMPLIFICATION
• COLON
• RAS
• INVASION
• GROWTH
• OVEREXPRESSION
• IDENTIFICATION

<jats:title>Abstract</jats:title><jats:p><jats:bold>Colorectal cancer (<jats:styled-content style="fixed-case">CRC</jats:styled-content>) is the third most common cancer in the <jats:styled-content style="fixed-case">USA</jats:styled-content>. <jats:styled-content style="fixed-case">MicroRNAs</jats:styled-content> play important roles in the pathogenesis of <jats:styled-content style="fixed-case">CRC</jats:styled-content>. In this study, we investigated the role of <jats:styled-content style="fixed-case">miR</jats:styled-content>‐30b in <jats:styled-content style="fixed-case">CRC</jats:styled-content> and found that its expression was significantly lower in <jats:styled-content style="fixed-case">CRC</jats:styled-content> tissues than that in normal tissues. We showed that a low expression level of <jats:styled-content style="fixed-case">miR</jats:styled-content>‐30b was closely related to poor differentiation, advanced <jats:styled-content style="fixed-case">TNM</jats:styled-content> stage and poor prognosis of <jats:styled-content style="fixed-case">CRC</jats:styled-content>. Further experiments showed that over‐expression of <jats:styled-content style="fixed-case">miR</jats:styled-content>‐30b suppressed <jats:styled-content style="fixed-case">CRC</jats:styled-content> cell proliferation <jats:italic>in vitro</jats:italic> and tumour growth <jats:italic>in vivo</jats:italic>. Specifically, <jats:styled-content style="fixed-case">miR</jats:styled-content>‐30b promoted <jats:styled-content style="fixed-case">G<jats:sub>1</jats:sub></jats:styled-content> arrest and induced apoptosis. Moreover, <jats:italic><jats:styled-content style="fixed-case">KRAS</jats:styled-content></jats:italic>, <jats:italic><jats:styled-content style="fixed-case">PIK3CD</jats:styled-content></jats:italic> and <jats:italic><jats:styled-content style="fixed-case">BCL2</jats:styled-content></jats:italic> were identified as direct and functional targets of <jats:styled-content style="fixed-case">miR</jats:styled-content>‐30b. <jats:styled-content style="fixed-case">MiR</jats:styled-content>‐30b directly targeted the 3′‐untranslated regions of their <jats:styled-content style="fixed-case">mRNAs</jats:styled-content> and repressed their expression. This study revealed functional and mechanistic links between <jats:styled-content style="fixed-case">miRNA</jats:styled-content>‐30b and oncogene <jats:styled-content style="fixed-case">KRAS</jats:styled-content>, <jats:styled-content style="fixed-case">PIK3CD</jats:styled-content> and <jats:styled-content style="fixed-case">BCL2</jats:styled-content> in the pathogenesis of <jats:styled-content style="fixed-case">CRC</jats:styled-content>. <jats:styled-content style="fixed-case">MiR</jats:styled-content>‐30b not only plays important roles in the regulation of cell proliferation and tumour growth in <jats:styled-content style="fixed-case">CRC</jats:styled-content>, but is also a potential prognostic marker or therapeutic target for <jats:styled-content style="fixed-case">CRC</jats:styled-content>. Restoration of <jats:styled-content style="fixed-case">miR</jats:styled-content>‐30b expression may represent a promising therapeutic approach for targeting malignant <jats:styled-content style="fixed-case">CRC</jats:styled-content>.

• 出版日期2014-3
• 单位南方医科大学