Targeting HCCR expression resensitizes gastric cancer cells to chemotherapy via down-regulating the activation of STAT3

• DOI: 10.1038/srep24196
• Publication Date: 2016-04-07T09:22:23Z
• Authors: Jun-Ling Zhang; Xiang-Zheng Liu; Peng-Yuan Wang; Guo-Wei Chen; Yong Jiang; Shu-Kai Qiao; Jing Zhu; Xin Wang; Yi-Sheng Pan; Yu-Cun Liu
• Keywords: Apoptosis; Cancer cell; Gene; STAT3; Cell growth; 0302 clinical medicine; oncogene; Internal medicine; Cancer; Microscopy, Confocal; Reverse Transcriptase Polymerase Chain Reaction; Life Sciences; Downregulation and upregulation; 3. Good health; Gene Expression Regulation, Neoplastic; Oncology; RNA Methylation and Modification in Gene Expression; Medicine; Cancer Therapy; RNA Interference; Fluorouracil; STAT3 Transcription Factor; Antimetabolites, Antineoplastic; Blotting, Western; Down-Regulation; Mice, Nude; Cancer research; Cell cycle; Article; Cell Line; 03 medical and health sciences; Stomach Neoplasms; Cell Line, Tumor; Proto-Oncogene Proteins; Biochemistry, Genetics and Molecular Biology; Health Sciences; Genetics; Animals; Humans; Molecular Biology; Biology; Oncogene; Cell Proliferation; Role of STAT3 in Cancer Inflammation and Immunity; The p53 Signaling Network in Cancer Research; RNAi Therapeutics; Gene Expression Regulation; Drug Resistance, Neoplasm; FOS: Biological sciences; Cell culture; Cell

AbstractThe 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.