miR-30a Suppresses Cell Migration and Invasion Through Downregulation of PIK3CD in Colorectal Carcinoma

Cellular Physiology and Biochemistry

关键词: miR-30a;    Colorectal carcinoma;    Migration;    Invasion;    PIK3CD;   

DOI  :  10.1159/000343362

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims MicroRNAs (miRNAs) play key roles in tumor metastasis. The aim of this study was to determine the regulation and function of miR-30a in colorectal carcinoma (CRC) metastasis. Methods The expression of miR-30a was detected in CRC cell lines and samples by qRT-PCR. The anti-metastatic effect of miR-30a was determined by both in vitro and in vivo assays. A luciferase reporter assay was performed to determine target association between miR-30a and phosphoinositide 3-kinase catalytic subunit delta (PIK3CD). Results miR-30a was significantly downregulated in highly metastatic CRC cell lines and metastatic tissues. Overexpression of miR-30a suppressed CRC cell migration and invasion in vitro and liver metastasis in vivo, whereas miR-30a deletion dramatically promoted cell migration and invasion. Further studies revealed that PIK3CD is a direct target of miR-30a as miR-30a bounds directly to the 3'-UTR of PIK3CD, subsequently reducing its expression. Similar to the restoring miR-30a expression, PIK3CD downregulation inhibited cell migration and invasion, whereas PIK3CD overexpression rescued the suppressive effect of miR-30a. Moreover, significant downregulation of miR-30a in metastatic CRC tissues was found to be inversely correlated with PIK3CD expression. Mechanistic studies revealed that miR-30a down-regulated the expression of key components of the Akt/mTOR pathway, whereas PIK3CD overexpression reversed this negative effect. Conclusion Our findings indicate that miR-30a might function as a metastasis suppressor in CRC. miR-30a may be a potential therapeutic target to block CRC metastasis.

【 授权许可】

CC BY-NC-ND