SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer.
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.
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
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Xu
Department of Gastrointestinal Surgery, Northern Jiangsu People's Hospital, Clinical Medical School, Yangzhou University, Yangzhou, People's Republic of China.
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Liu
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
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Xia
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
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Yin
Clinical Medical Examination Center, Northern Jiangsu People's Hospital, Clinical Medical School, Yangzhou University, Yangzhou, People's Republic of China.
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Kong
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
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Chen
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, People's Republic of China.
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Huang
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
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Shu
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
C493956:CDKN1A protein, human; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D050759:Cyclin-Dependent Kinase Inhibitor p21; D003598:Cytoskeletal Proteins; C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; C492185:STAU1 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human