1. SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer.
- Author
-
Xu TP, Liu XX, Xia R, Yin L, Kong R, Chen WM, Huang MD, and Shu YQ
- Subjects
- Cell Line, Tumor, 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 genetics, RNA, Long Noncoding genetics, RNA, Messenger genetics, RNA, Neoplasm genetics, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Sp1 Transcription Factor genetics, Stomach Neoplasms genetics, Stomach Neoplasms pathology, Apoptosis, Cell Proliferation, Kruppel-Like Transcription Factors biosynthesis, RNA Stability, RNA, Long Noncoding biosynthesis, RNA, Messenger metabolism, RNA, Neoplasm metabolism, Sp1 Transcription Factor metabolism, Stomach Neoplasms metabolism
- 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.
- Published
- 2015
- Full Text
- View/download PDF