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Open Access 01-12-2017 | Research

KCNMA1 cooperating with PTK2 is a novel tumor suppressor in gastric cancer and is associated with disease outcome

Authors: Gaoxiang Ma, Hanting Liu, Qiuhan Hua, Meilin Wang, Mulong Du, Yadi Lin, Yuqiu Ge, Weida Gong, Qinghong Zhao, Fulin Qiang, Guoquan Tao, Zhengdong Zhang, Haiyan Chu

Published in: Molecular Cancer | Issue 1/2017

Abstract

Background

Inactivation of tumor suppressor genes by promoter hypermethylation plays a key role in the tumorgenesis. It is necessary to uncover the detailed pattern of whole genome-wide abnormal DNA methylation during the development of gastric cancer (GC).

Method

We performed a genome-wide methylation detection using 12 paired of GC tissues and their corresponding normal tissues. Methylation-specific PCR (MSP) and bisulphite sequencing (BSP) were used to measure methylation status of specific CpG site. Based on the bioinformatic analysis, the cell phenotypes and mouse model experiments were constructed to detect effect of the target gene. Using the Kaplan–Meier survival curve, the clinical value of KCNMA1 was assessed in GC patients.

Results

The CpG site cg24113782 located at the promoter of KCNMA1 showed the most significant difference, contributing to the commonly silenced KCNMA1in gastric cancer cells and primary GC tissues. The promoter methylation of KCNMA1 was detected in 68.7% (77/112) of tumor tissues, compared with 16.2% (18/112) of normal tissues (P < 0.001). The survival curve indicated that KCNMA1 hypermethylation was significantly associated with the shortened survival in GC patients (P = 0.036). KCNMA1 significantly inhibited biological malignant behavior of gastric cancer cell by inducing cell apoptosis in vitro, and suppressed xenograft tumor growth in subcutaneous mouse models (both P < 0.001). Furthermore, the anti-tumor effect of KCNMA1was mediated through suppressing the expression of PTK2.

Conclusion

KCNMA1 is a critical tumor suppressor in gastric carcinogenesis and its hypermethylation is an independent prognostic factor in patients with gastric cancer.

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Title: KCNMA1 cooperating with PTK2 is a novel tumor suppressor in gastric cancer and is associated with disease outcome
Authors: Gaoxiang Ma
Hanting Liu
Qiuhan Hua
Meilin Wang
Mulong Du
Yadi Lin
Yuqiu Ge
Weida Gong
Qinghong Zhao
Fulin Qiang
Guoquan Tao
Zhengdong Zhang
Haiyan Chu
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-017-0613-z

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Abstract

Background

Method

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