SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer

T-P Xu; X-X Liu; R Xia; L Yin; R Kong; W-M Chen; M-D Huang; Y-Q Shu

doi:10.1038/onc.2015.18

SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer

Oncogene. 2015 Nov 5;34(45):5648-61. doi: 10.1038/onc.2015.18. Epub 2015 Mar 2.

Authors

T-P Xu¹, X-X Liu², R Xia¹, L Yin¹, R Kong³, W-M Chen¹, M-D Huang⁴, Y-Q Shu¹

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
² Department of Gastrointestinal Surgery, Northern Jiangsu People's Hospital, Clinical Medical School, Yangzhou University, Yangzhou, People's Republic of China.
³ Clinical Medical Examination Center, Northern Jiangsu People's Hospital, Clinical Medical School, Yangzhou University, Yangzhou, People's Republic of China.
⁴ Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, People's Republic of China.

PMID: 25728677
DOI: 10.1038/onc.2015.18

Abstract

The long noncoding RNA TINCR shows aberrant expression in human squamous carcinomas. However, its expression and function in gastric cancer remain unclear. We report that TINCR is strongly upregulated in human gastric carcinoma (GC), where it was found to contribute to oncogenesis and cancer progression. We also revealed that TINCR overexpression is induced by nuclear transcription factor SP1. Silencing TINCR expression inhibited cell proliferation, colony formation, tumorigenicity and apoptosis promotion, whereas TINCR overexpression promoted cell growth, as documented in the SGC7901 and BGC823 cell lines. Mechanistic analyses indicated that TINCR could bind to STAU1 (staufen1) protein, and influence KLF2 mRNA stability and expression, then KLF2 regulated cyclin-dependent kinase genes CDKN1A/P21 and CDKN2B/P15 transcription and expression, thereby affecting the proliferation and apoptosis of GC cells. Together, our findings suggest that TINCR 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

Apoptosis*
Cell Line, Tumor
Cell Proliferation*
Cyclin-Dependent Kinase Inhibitor p15 / genetics
Cyclin-Dependent Kinase Inhibitor p15 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / genetics
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Cytoskeletal Proteins / genetics
Cytoskeletal Proteins / metabolism
Humans
Kruppel-Like Transcription Factors / biosynthesis*
Kruppel-Like Transcription Factors / genetics
RNA Stability*
RNA, Long Noncoding / biosynthesis*
RNA, Long Noncoding / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism*
RNA, Neoplasm / genetics
RNA, Neoplasm / metabolism*
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism
Sp1 Transcription Factor / genetics
Sp1 Transcription Factor / metabolism*
Stomach Neoplasms / genetics
Stomach Neoplasms / metabolism*
Stomach Neoplasms / pathology

Substances

CDKN1A protein, human
CDKN2B protein, human
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p21
Cytoskeletal Proteins
KLF2 protein, human
Kruppel-Like Transcription Factors
RNA, Long Noncoding
RNA, Messenger
RNA, Neoplasm
RNA-Binding Proteins
STAU1 protein, human
Sp1 Transcription Factor
SP1 protein, human