Cancer Communications
indexed by SCI
BMC

Original article
DUXAP8, a pseudogene derived lncRNA, promotes growth of pancreatic carcinoma cells by epigenetically silencing CDKN1A and KLF2
Yifan Lian, Jiebin Yang, Yikai Lian, Chuangxing Xiao, Xuezhen Hu and Hongzhi Xu
Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, 361005, Fujian, P. R. China
[Abstract]

Background
Recent studies highlight pseudogene derived long non-coding RNAs (lncRNAs) as key regulators of cancer biology. However, few of them have been well characterized in pancreatic cancer. Here, we aimed to identify the association between pseudogene derived lncRNA DUXAP8 and growth of pancreatic cancer cells.
Methods
We screened for pseudogene derived lncRNAs associated with human pancreatic cancer by comparative analysis of three independent datasets from GEO. Quantitative real-time reverse transcription polymerase chain reaction was used to assess the relative expression of DUXAP8 in pancreatic cancer tissues and cells. Loss-of-function approaches were used to investigate the potential functional roles of DUXAP8 in pancreatic cancer cell proliferation and apoptosis in vitro and in vivo. RNA immunoprecipitation, chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of DUXAP8 with target proteins and genes in pancreatic cancer cells.
Results
Pancreatic cancer tissues had significantly higher DUXAP8 levels than paired adjacent normal tissues. High DUXAP8 expression was associated with a larger tumor size, advanced pathological stage and shorter overall survival of pancreatic cancer patients. Moreover, silencing DUXAP8 expression by siRNA or shRNA inhibited pancreatic cancer cell proliferation and promoted apoptosis in vitro and in vivo. Mechanistic analyses indicated that DUXAP8 regulates PC cell proliferation partly through downregulation of tumor suppressor CDKN1A and KLF2 expression.
Conclusion
Our results suggest that tumor expression of pseudogene derived lncRNA DUXAP8 plays an important role in pancreatic cancer progression. DUXAP8 may serve as a candidate biomarker and represent a novel therapeutic target of pancreatic cancer.
Cancer Communications   Epub date: 10/30/2018   doi:10.1186/s40880-018-0333-9   [ PDF Full-text ]   

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