LncRNA CTD-3252C9.4 modulates pancreatic cancer cell survival and apoptosis through regulating IFI6 transcription.
Xin Yin, Jingyan Yang, Jintian Chen, Ruiqi Ni, Yanhao Zhou, Hao Song, Liang Jin, Tingting Tang, Yi Pan
Author Information
Xin Yin: Center for Genetic Medicine, Xuzhou Maternity and Child Health Care Hospital, 46 Heping Road, Xuzhou, Jiangsu, China.
Jingyan Yang: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang Avenue, Nanjing, Jiangsu, China.
Jintian Chen: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang Avenue, Nanjing, Jiangsu, China.
Ruiqi Ni: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang Avenue, Nanjing, Jiangsu, China.
Yanhao Zhou: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang Avenue, Nanjing, Jiangsu, China.
Hao Song: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang Avenue, Nanjing, Jiangsu, China.
Liang Jin: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang Avenue, Nanjing, Jiangsu, China. ljstemcell@cpu.edu.cn.
Tingting Tang: Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, Jiangsu, China. TTT@xzhmu.edu.cn.
Yi Pan: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang Avenue, Nanjing, Jiangsu, China. panyi@cpu.edu.cn. ORCID
BACKGROUND: Pancreatic cancer (PC) is one of the most lethal cancer types with high degree of malignancy and poor prognosis. Recent studies have shown that long non-coding RNAs (lncRNAs) were associated with the initiation and progression of pancreatic cancer. In the current study, we have investigated the expression, biological function and mechanism of a lncRNA CTD-3252C9.4 in pancreatic cancer. METHODS: The expression of CTD-3252C9.4 in pancreatic cancer cells and tissues was measured by qRT-PCR. In vitro and in vivo functional experiments assays were implemented for identifying CTD-3252C9.4 function in pancreatic cancer. Molecular relationships among CTD-3252C9.4, IRF1 and IFI6 were investigated via luciferase reporter assay, pulldown assay and ChIP assays. RESULTS: CTD-3252C9.4 was found remarkably decreased in pancreatic cancer cells and tissues. Overexpression of CTD-3252C9.4 suppressed migration, invasion and proliferation, yet facilitated apoptosis of pancreatic cancer cells both in vitro and in vivo. Then, IFI6 was identified as a downstream target that could be down-regulated by CTD-3252C9.4 and IFI6 overexpression could counteract the effects of CTD-3252C9.4 upregulation on the survival and apoptosis of pancreatic cancer cells. Furthermore, mechanism experiments revealed that IRF1 was a transcriptional factor of IFI6 that can be blocked by CTD-3252C9.4 to inhibit IFI6 transcription. CONCLUSION: Our data indicated that CTD-3252C9.4 could promote pancreatic cancer cell apoptosis and restrain cell growth via binding IRF1 and preventing the transcription of IFI6, which may become a potential therapeutic target for pancreatic cancer.
