Up-regulated miR-199a-5p in gastric cancer functions as an oncogene and targets klotho

BMC Cancer

Hou-Quan Tao¹  Zhi-Ming Hu⁴  Hua-Ping Wang⁴  Liang Tao⁴  Yi-Ding Lu⁴  Xiao-Ting Jiang³  Sheng Yu⁵  Ying-Yu Ma²  Xu-Jun He⁴ 

[1]Department of Gastrointestinal Surgery, Zhejiang Provincial People’s Hospital, Hangzhou 310014, China

[2]Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, Hangzhou 310014, China

[3]Clinical Laboratory, Zhejiang Provincial People’s Hospital, Hangzhou 310014, China

[4]Department of Surgery, Haining No.3 People’s Hospital, Haining 314408, Zhejiang Province, China

[5]Wenzhou Medical College, Wenzhou 310025, Zhejiang Province, China

关键词: Klotho;    Target gene;    Gastric cancer;    Oncogene;    miR-199a-5p;   

Others  :  858939
DOI  :  10.1186/1471-2407-14-218

 received in 2013-09-18, accepted in 2014-03-12,  发布年份 2014

【 摘 要 】

Background

Recent studies have shown that miR-199a-5p plays opposite roles in cancer initiation and progression of different cancer types, acting as oncogene for some cancer types but as tumor suppressor gene for others. However, the role and molecular mechanism of miR-199a-5p in gastric cancer are largely unknown.

Methods

In this study, miR-199a-5p expression level in gastric cancer was first analyzed by qPCRand then validated in 103 gastric cancer patients by in situ hybridization (ISH). Gastric cancer cell lines were transfected with miR-199a-5p inhibitor and mimic, and underwent in vitro transwell assays. Target genes (klotho) were identified using Luciferase reporter assay. Immunohistochemical staining was also used to investigate on how miR-199a-5p regulates the tumour-suppressive effects of klotho in gastric cancer.

Results

In our present study, we found that miR-199a-5p level was significantly increased in gastric cancer tissues compared to paired normal tissues. We observed that miR-199a-5p could promote migration and invasion of gastric cancer cells. In situ hybridization of miR-199a-5p also confirmed that higher miR-199a-5p expression level was associated with increased likelihood of lymph node metastasis and later TNM stage. Luciferase reporter assay and immunohistochemistry revealed that klotho might be the downstream target of miR-199a-5p.

Conclusions

Our present study suggests that miR-199a-5p acts as an oncogene in gastric cancer and functions by targeting klotho.

【 授权许可】

   
2014 He et al.; licensee BioMed Central Ltd.

【 图 表 】

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