E2F1 induces TINCR transcriptional activity and accelerates gastric cancer progression via activation of TINCR/STAU1/CDKN2B signaling axis

Tong-Peng Xu; Yan-Fen Wang; Wei-Liang Xiong; Pei Ma; Wen-Yu Wang; Wen-Ming Chen; Ming-De Huang; Rui Xia; Rong Wang; Er-Bao Zhang; Yan-Wen Liu; Wei De; Yong-Qian Shu

doi:10.1038/cddis.2017.205

E2F1 induces TINCR transcriptional activity and accelerates gastric cancer progression via activation of TINCR/STAU1/CDKN2B signaling axis

Cell Death Dis. 2017 Jun 1;8(6):e2837. doi: 10.1038/cddis.2017.205.

Authors

Tong-Peng Xu¹, Yan-Fen Wang², Wei-Liang Xiong³, Pei Ma¹, Wen-Yu Wang¹, Wen-Ming Chen⁴, Ming-De Huang⁵, Rui Xia⁶, Rong Wang¹, Er-Bao Zhang⁷, Yan-Wen Liu⁷, Wei De⁷, Yong-Qian Shu¹

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
² Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, P.R. China.
³ State Key Laboratory of Microbial Metabolism, and School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, P.R. China.
⁴ Department of Oncology, Jining No.1 People's Hospital, Jining City, China.
⁵ Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an City, P.R. China.
⁶ Department of Medical Laboratory, Nanjing Chest Hospital, Nanjing, P.R. China.
⁷ Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, P.R. China.

Abstract

Recent evidence indicates that E2F1 transcription factor have pivotal roles in the regulation of cellular processes, and is found to be dysregulated in a variety of cancers. Long non-coding RNAs (lncRNAs) are also reported to exert important effect on tumorigenesis. E2F1 is aberrantly expressed in gastric cancer (GC), and biology functions of E2F1 in GC are controversial. The biological characteristics of E2F1 and correlation between E2F1 and lncRNAs in GC remain to be found. In this study, integrated analysis revealed that E2F1 expression was significantly increased in GC cases and its expression was positively correlated with the poor pathologic stage, large tumor size and poor prognosis. Forced E2F1 expression promotes proliferation, whereas loss of E2F1 function decreased cell proliferation by blocking of cell cycle in GC cells. Mechanistic analyses indicated that E2F1 accelerates GC growth partly through induces TINCR transcription. TINCR could bind to STAU1 (staufen1) protein, and influence CDKN2B mRNA stability and expression, thereby affecting the proliferation of GC cells. Together, our findings suggest that E2F1/TINCR/STAU1/CDKN2B signaling axis contributes to the oncogenic potential of GC and may constitute a potential therapeutic target in this disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / genetics*
Adenocarcinoma / metabolism
Adenocarcinoma / mortality
Adenocarcinoma / pathology
Animals
Carcinogenesis / genetics
Carcinogenesis / metabolism
Carcinogenesis / pathology
Cell Cycle Checkpoints
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p15 / genetics*
Cyclin-Dependent Kinase Inhibitor p15 / metabolism
Cytoskeletal Proteins / genetics*
Cytoskeletal Proteins / metabolism
Disease Progression
E2F1 Transcription Factor / genetics*
E2F1 Transcription Factor / metabolism
Gene Expression Regulation, Neoplastic*
Humans
Mice
Mice, Nude
Neoplasm Transplantation
Prognosis
Protein Binding
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA-Binding Proteins / genetics*
RNA-Binding Proteins / metabolism
Signal Transduction
Stomach Neoplasms / genetics*
Stomach Neoplasms / metabolism
Stomach Neoplasms / mortality
Stomach Neoplasms / pathology
Survival Analysis
Transcription, Genetic

Substances

CDKN2B protein, human
Cyclin-Dependent Kinase Inhibitor p15
Cytoskeletal Proteins
E2F1 Transcription Factor
E2F1 protein, human
RNA, Long Noncoding
RNA, Messenger
RNA-Binding Proteins
STAU1 protein, human
TINCR lncRNA, human