The role of microRNA-133b and its target gene FSCN1 in gastric cancer

Journal of Experimental & Clinical Cancer Research

Jinsheng He¹  Qi Zhou⁵  Pengfei He²  Jiaqiang Huang¹  Jie Liu⁴  Tao Hong¹  Dongling Zou⁵  Hua Bai³  Lihua Guo¹ 

[1] College of Life Sciences and Bioengineering, Beijing Jiaotong University, Shangyuan Residence, Beijing 100044, Haidian District, China;National Institutes for Food and Drug Control, No.2 Tiantan Xi Li, Beijing 100050, China;Department of Ophthalmology, General Hospital of Bei Jing Command of PLA, #5 Nanmencang, Beijing 100700, DongCheng District, China;School of Computer and Information Technology, Shangyuan Residence, Beijing 100044, Haidian District, China;Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing 400030, China

关键词: Tumor suppressor;    FSCN1;    miR-133b;    Gastric cancer;   

Others  :  1145493
DOI  :  10.1186/s13046-014-0099-0

 received in 2014-07-07, accepted in 2014-11-17,  发布年份 2014

【 摘 要 】

Background

Increasing evidences have documented that microRNAs (miRNAs) act as oncogenes or tumor suppressors in gastric cancer (GC). In this study, we aimed to investigate the expression of miR-133b in a large number of GC samples and elucidate its role in GC carcinogenesis and the detailed mechanism.

Methods

We used Taqman probe stem-loop real-time PCR to accurately measure the levels of miR-133b in 100 pairs of gastric cancer tissues and the adjacent non-neoplastic tissues. miR-133b mimics were overexpressed in GC cell lines, miR-133b inhibitors were also introduced in GES cells to investigate its role on regulating cell proliferation, cell migration and cell invasion. The target of miR-133b was identified by luciferase reporter assay and western blot. Fascin actin-bundling protein 1 (FSCN1) siRNA was used to achieve the knockdown of FSCN1 in GC cells and to investigate its role on modulating GC cell proliferation and invasion.

Results

miR-133b was significantly down-regulated in GC cell lines and in GC tissues compared with adjacent normal tissues. Moreover, lower-level of miR-133b was also associated with venous invasion and a more aggressive tumor phenotype. Re-introduction of miR-133b in GC cells can inhibit cell proliferation, cell migration and invasion. In contrary, knockdown of miR-133b in GES cells can promote cell proliferation and invasion. Further investigation indicated that miR-133b targeted FSCN1 in GC cells and knockdown of FSCN1 can also inhibit GC cell growth and invasion.

Conclusion

Our findings demonstrated that miR-133b was significantly down-regulated in GC tissues and exerted its tumor suppressor role in GC cells. The investigation of the detailed mechanism showed that miR-133b directly targeted FSCN1 which functioned as an oncogenic gene in GC cells. These results suggested that miR-133b can be developed as a new diagnostic marker or therapeutic target for GC.

【 授权许可】

   
2014 Guo et al.; licensee BioMed Central Ltd.

【 图 表 】

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