Cancer Management and Research (Nov 2018)
Inhibition of long non-coding RNA HOTAIR enhances radiosensitivity via regulating autophagy in pancreatic cancer
Abstract
Chunli Wu,1–3 Liang Yang,4 Xun Qi,2 Taifang Wang,3 Meng Li,3 Ke Xu1,2 1Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China; 2Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, China; 3Department of Radiation Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China; 4Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China Background: Resistance to radiation therapy is still a challenge for treatment of pancreatic cancer (PC). Long non-coding RNAs (lncRNA) HOTAIR has been found to play a oncogenic role in several cancers. However, the correlation between HOTAIR and radiotherapy in PC is still unclear.Methods: TCGA data was collected to analyze the expression of HOTAIR and its relationship with PC progression. A series of functional experiments were conducted to explore the role of HOTAIR in PC radiosensitivity and its underlying molecular mechanisms.Results: By the analysis of the TCGA data, we found HOTAIR expression in PC tissues was significantly higher than normal tissues and associated with tumor progression. The function analysis showed HOTAIR was enriched in biological regulation and response to stimulus.And in vitro study, the expression of HOTAIR was increased in PANC-1 and AsPC-1 cells after radiation. We identified that HOTAIR knockdown could enhance radiosensitivity and influence autophagy by up-regulating ATG7 expression in PC cells. By futher rescue experiments using rapamycin, activation of autophagy could reversed the the inhibition of cell proliferation and colony formation, as well as promotion of apoptosis mediated by HOTAIR knockdown, indicating that HOTAIR knockdown promoted radiosensitivity of PC cells by regulating autophagy. Conclusion: Our finding revealed the the regulatory role of HOTAIR in radiosensitivity and provided a a new sight to improve radiotherapy effciency in PC. Keywords: HOTAIR, pancreatic cancer, radiosensitivity, autophagy, Atg7
