Peptidylarginine deiminase IV promotes the development of chemoresistance through inducing autophagy in hepatocellular carcinoma

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• 作者：Tingting Fan (4)
  Changsong Zhang (5) (6)
  Ming Zong (4)
  Qiudong Zhao (6)
  Xue Yang (6)
  Chong Hao (6)
  Hui Zhang (4)
  Shanshan Yu (4)
  Jinhu Guo (4)
  Ruhan Gong (4)
  Shasha Fan (4)
  Lixin Wei (6)
  Lieying Fan (4)
  
  4. Department of Clinical Laboratory ; Shanghai East Hospital ; Tongji University Medical School ; No. 150 ; Jimo Road ; Shanghai ; 200120 ; China
  5. Clinical Oncology Laboratory ; Changzhou cancer Hospital of Soochow University ; Changzhou ; 213001 ; China
  6. Tumor Immunology and Gene Therapy Center ; Eastern Hepatobiliary Surgery Hospital ; Second Military Medical University ; 225 Changhai Road ; Shanghai ; 200438 ; China
  
• 关键词：PADI4 ; Autophagy ; Hepatocellular Carcinoma ; Chemoresistance
• 刊名：Cell & Bioscience
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：4
• 期：1
• 全文大小：1,662 KB
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• 刊物主题：Cell Biology; Microbiology;
• 出版者：BioMed Central
• ISSN：2045-3701

文摘

Background Peptidylarginine deiminase IV (PADI4) is widely distributed in several tissues and the expression is correlated with many pathological processes. Chemotherapy remains a major treatment alternatively to surgery for a large number of patients at the advanced stage of hepatocellular carcinoma (HCC). However, the role of PADI4 in the chemoresistance of HCC has not been identified. Methods MTT and PI/Annexin V assay were employed to examine the proliferation and apoptosis of HCC cell lines. The expression of MDR1 is detected by Realtime PCR. GFP tagged LC3 expression vector and electron microscopy are utilized to demonstrate the occurrence of autophagy. Results We observed that the elevated PADI4 expression is associated with chemoresistance in HCC patients with TACE after surgery. In addition, we found that overexpression of PADI4 in HCC cell lines lead to the resistance to chemotherapeutic agents in vitro and in vivo. Interestingly, the HCC cells that overexpressed PADI4 were observed to undergo autophagy which was known as a protective mechanism for cells to resist the cell tosicity from chemotherapy. Autophagy inhibitor could effectively restore the sensitivity of HCC cells to chemotherapy in vitro and in vivo. Conclusions These results indicate that PADI4 may induce chemoresistance in HCC cells by leading autophagy.