title: Targeting HCCR expression resensitizes gastric cancer cells to chemotherapy via down-regulating the activation of STAT3.
abstract: The human cervical cancer oncogene (HCCR) has been found to be overexpressed in a variety of human cancers. However, the level of expression of HCCR and its biological function in gastric cancer are largely unknown. In this study, we evaluated HCCR expression in several gastric cancer cell lines and in one normal gastric mucosal cell line. We established a 5-FU-resistant gastric cancer cell subline, and we evaluated its HCCR expression. HCCR expression levels were high in gastric cancer lines, and expression was significantly increased in the 5-FU-resistant cancer cell subline. HCCR expression affected cell growth by regulating apoptosis in the cancer cells, and it had a positive correlation with p-STAT3 expression. Western blot and luciferase reporter assays showed that the activation of STAT3 upregulated HCCR expression in a positive feedback loop model. In vivo and in vitro studies showed that HCCR plays an important role in the apoptosis induced by 5-FU. Our data demonstrate that HCCR is probably involved in apoptosis and cancer growth and that it functions as a p-STAT3 stimulator in a positive feedback loop model. In gastric cancer cells, HCCR confers a more aggressive phenotype and resistance to 5-FU-based chemotherapy.
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Xiang-Zheng
authors.initials: XZ
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, P. R. China.
authors.forename: Shu-Kai
authors.initials: SK
authors.lastname: Qiao
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Pan
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Yu-Cun
authors.initials: YC
authors.lastname: Liu
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D018613:Microscopy, Confocal; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; C476732:LETMD1 protein, human; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; D005472:Fluorouracil