Oncotarget

Research Papers:

Long noncoding RNA OR3A4 promotes metastasis and tumorigenicity in gastric cancer

Xiaobo Guo, Ziguo Yang, Qiaoming Zhi _, Dan Wang, Lei Guo, Guimei Li, Ruizhen Miao, Yulong Shi and Yuting Kuang

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Oncotarget. 2016; 7:30276-30294. https://doi.org/10.18632/oncotarget.7217

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Abstract

Xiaobo Guo1, Ziguo Yang1, Qiaoming Zhi2, Dan Wang3, Lei Guo5, Guimei Li4, Ruizhen Miao1, Yulong Shi1, Yuting Kuang2

1Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China

2Departments of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China

3Departments of Science and Education, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China

4Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China

5Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China

Correspondence to:

Qiaoming Zhi, email: [email protected]

Guimei Li, email: [email protected]

Dan Wang, email: [email protected]

Keywords: gastric cancer, lncRNA, metastasis, OR3A4, tumorigenesis

Received: July 12, 2015     Accepted: January 26, 2016     Published: February 06, 2016

ABSTRACT

The contribution of long noncoding RNAs (lncRNAs) to metastasis of gastric cancer remains largely unknown. We used microarray analysis to identify lncRNAs differentially expressed between normal gastric tissues and gastric cancer tissues and validated these differences in quantitative real-time (qRT)-PCR experiments. The expression levels of lncRNA olfactory receptor, family 3, subfamily A, member 4 (OR3A4) were significantly associated with lymphatic metastasis, the depth of cancer invasion, and distal metastasis in 130 paired gastric cancer tissues. The effects of OR3A4 were assessed by overexpressing and silencing OR3A4 in gastric cancer cells. OR3A4 promoted cancer cell growth, angiogenesis, metastasis, and tumorigenesis in vitro and in vivo. Global microarray analysis combined with RT-PCR, RNA immunoprecipitation, and RNA pull-down analyses after OR3A4 transfection demonstrated that OR3A4 influenced biologic functions in gastric cancer cells via regulating the activation of PDLIM2, MACC1, NTN4, and GNB2L1. Our results reveal OR3A4 as an oncogenic lncRNA that promotes tumor progression, Therefore, lncRNAs might function as key regulatory hubs in gastric cancer progression.


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