Research Papers:

ISL1, a novel regulator of CCNB1, CCNB2 and c-MYC genes, promotes gastric cancer cell proliferation and tumor growth

Qiong Shi, Weiping Wang, Zhuqing Jia, Ping Chen, Kangtao Ma and Chunyan Zhou _

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Oncotarget. 2016; 7:36489-36500. https://doi.org/10.18632/oncotarget.9269

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Qiong Shi1,*, Weiping Wang1,*, Zhuqing Jia1, Ping Chen1, Kangtao Ma1, Chunyan Zhou1

1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing, P.R. China

*These authors contributed equally to this work

Correspondence to:

Chunyan Zhou, email: [email protected]

Keywords: ISL1, gastric cancer, proliferation, CCNB, c-MYC

Received: October 05, 2015     Accepted: April 22, 2016     Published: May 10, 2016


Islet-1 (ISL1) belongs to the LIM homeodomain transcription factor family, which is specifically expressed in certain tissue types only. Previously, we reported that ISL1 is aberrantly overexpressed in gastric cancer (GC). However, its role in GC is not clear. Here, we report that ISL1 is aberrantly upregulated not only in human gastric carcinoma tissues but also in some GC cell lines. Upregulated ISL1 expression enhanced xenografted gastric carcinoma development, while ISL1 knockdown inhibited GC growth in nude mice. ISL1 overexpression promoted GC cell proliferation, colony formation, and cell growth in soft agar, and facilitated cell cycle transition in GC cells, demonstrated an increase in the proportion of cells in the G2/M and S phases and a decrease in the proportion of cells in the G1 phase. Furthermore, we provide evidence that ISL1 is a novel regulator of the cyclin B1 (CCNB1), cyclin B2 (CCNB2) and c-myc (c-MYC) genes. ISL1 activated the expression of these genes in GC cells by binding to the conserved binding sites on their promoters or enhancers. The expression levels of the genes were decreased in response to ISL1 knockdown. Therefore, ISL1 may serve as a potential therapeutic target in GC.

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