Open Access Highly Accessed Research article

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

Xu-Jun He14, Ying-Yu Ma1, Sheng Yu2, Xiao-Ting Jiang3, Yi-Ding Lu4, Liang Tao4, Hua-Ping Wang4, Zhi-Ming Hu4* and Hou-Quan Tao15*

Author Affiliations

1 Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, Hangzhou 310014, China

2 Wenzhou Medical College, Wenzhou 310025, Zhejiang Province, 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 Department of Gastrointestinal Surgery, Zhejiang Provincial People’s Hospital, Hangzhou 310014, China

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BMC Cancer 2014, 14:218  doi:10.1186/1471-2407-14-218

Published: 24 March 2014



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.


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.


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.


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

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