title: Positive feedback loop of IL-1β/Akt/RARα/Akt signaling mediates oncogenic property of RARα in gastric carcinoma.
abstract: Abnormal expression and function of retinoic acid receptor α (RARα) have been reported to be associated with various cancers including acute promyelocytic leukemia and hepatocellular carcinoma. However, the role and the mechanism of RARα in gastric carcinoma (GC) were unknown. Here, the expression of RARα was frequently elevated in human GC tissues and cell lines, and its overexpression was closely correlated with tumor size, lymph node metastasis and clinical stages in GC patients. Moreover, RARα overexpression was related with pathological differentiation. Functionally, RARα knockdown inhibited the proliferation and metastasis of GC cells, as well as enhanced drug susceptibility both in vitro and in vivo. Additionally, RARα knockdown suppressed GC progression through regulating the expression of cell proliferation, cell cycle, invasion and drug resistance associated proteins, such as PCNA, CyclinB1, CyclinD2, CyclinE, p21, MMP9 and MDR1. Mechanistically, the above oncogenic properties of RARα in GC were closely associated with Akt signaling activation. Moreover, overexpression of RARα was induced by IL-1β/Akt signaling activation, which suggested a positive feedback loop of IL-1β/Akt/RARα/Akt signaling in GC. Taken together, we demonstrated that RARα was frequently elevated in GC and exerted oncogenic properties. It might be a potential molecular target for GC treatment.
authors.affiliation: Department of Pathology, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou 363000, Fujian Province, China.
authors.forename: Hong-Yue
authors.initials: HY
authors.lastname: Ren
authors.affiliation: Department of Medical College, Xiamen University, Xiamen 361005, Fujian Province, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Department of Life Sciences, Xiamen University, Xiamen 361005, Fujian Province, China.
authors.forename: Gui-Li
authors.initials: GL
authors.lastname: Huang
authors.affiliation: Department of Biobank, The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biobank, The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian Province, China.
authors.forename: Jin-Xing
authors.initials: JX
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Department of Life Sciences, Xiamen University, Xiamen 361005, Fujian Province, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Gastroenterology Institute of Xiamen University, Gastroenterology Center of Xiamen, Xiamen 361003, Fujian Province, China.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Liu
authors.affiliation: Department of Biobank, The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian Province, China.
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Shen
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D025461:Feedback, Physiological; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D000072482:Retinoic Acid Receptor alpha / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D018797:Cell Cycle Proteins; C508585:IL1B protein, human; D053583:Interleukin-1beta; C000607071:RARA protein, human; D000072482:Retinoic Acid Receptor alpha; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil
keywords: Akt; IL-1β; RARα; gastric carcinoma