Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2

Journal of Translational Medicine

Jirong Huo²  Youshuo Liu¹  Yonghong Guo¹  Hongyi Zhu²  Guoqing Huang³  Limin Long¹ 

[1] Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China;Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China;Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China

关键词: MicroRNA138;    Biomarker;    Metastasis;    Colorectal cancer;   

Others  :  824748
DOI  :  10.1186/1479-5876-11-275

 received in 2013-08-22, accepted in 2013-10-18,  发布年份 2013

【 摘 要 】

Background

Colorectal cancer (CRC) is the most common digestive system malignancy. The molecular events involved in the development and progression of CRC remain unclear. Recently, more and more evidences have showed that deregulated miRNAs participate in colorectal carcinogenesis.

Methods

The expression levels of miR-138 were first examined in CRC cell lines and tumor tissues by real-time PCR. The in vitro and in vivo functional effects of miR-138 were examined further. Luciferase reporter assays were conducted to confirm the targeting associations. Kaplan-Meier analysis and log-rank tests were performed to estimate the overall survival and disease free survival rate.

Results

miR-138 was found to be down-regulated in human colorectal cancer tissues and cell lines. Ectopic expression of miR-138 resulted in a dramatic inhibition of CRC migration and invasion in vitro and in vivo. Twist basic helix-loop-helix transcription factor 2 gene (TWIST2) was identified as one of the functional target. Restoration of miR-138 resulted in a dramatic reduction of the expression of TWIST2 at both mRNA and protein levels by directly targeting its 3′-untranslated region (3′UTR). Up-regulation of TWIST2 was detected in CRC tumors compared with adjacent normal tissues (P < 0.001) and is inversely correlated with miR-138 expression. We also identified that down-regulation of miR-138 was associated with lymph node metastasis, distant metastasis, and always predicted poor prognosis.

Conclusion

These data highlight a pivotal role for miR-138 in the regulation of CRC metastasis by targeting TWIST2, and suggest a potential application of miR-138 in prognosis prediction and CRC treatment.

【 授权许可】

   
2013 Long et al.; licensee BioMed Central Ltd.

【 图 表 】

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