title: Downregulation of Rap1 promotes 5-fluorouracil-induced apoptosis in hepatocellular carcinoma cell line HepG2.
abstract: Recent studies have revealed that repressor/activator protein (Rap1) not only protects telomeres from sister chromatid exchange, but also functions in genomewide transcriptional regulation. Knockdown of Rap1 sensitizes breast cancer cells to adriamycin-induced apoptosis. However, little is known about the role of Rap1 in the progression of hepatocellular carcinoma (HCC). The present study aimed to investigate the functions of Rap1 in HCC progression and to determine whether targeting the Rap1 signaling pathway may be of therapeutic value against HCC. We found knockdown of Rap1 by microRNA (miRNA) interference enhanced significantly apoptosis and 5-fluorouracil (5-FU) chemosensitivity in HepG2 cell line. Rap1 miRNA downregulated nuclear factor-κB p65 (NF-κB p65) expression, and upregulated inhibitor of NF-κB (IκB) expression. In vivo, Rap1 miRNA combined with 5-FU treatment led to a significant reduction of tumor growth as compared with 5-FU alone. The results indicate that Rap1 miRNA can effectively enhance sensitivity of HepG2 cell line to 5-FU chemotherapy in vitro and in vivo.
authors.affiliation: Department of Abdominal Surgery, Yunnan Cancer Hospital (The Third Affiliated Hospital, Kunming Medical University), Kunming, Yunnan 650118, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zha
authors.affiliation: Department of Abdominal Surgery, Yunnan Cancer Hospital (The Third Affiliated Hospital, Kunming Medical University), Kunming, Yunnan 650118, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gan
authors.affiliation: Yunnan Cancer Research Institute, Yunnan Cancer Hospital (The Third Affiliated Hospital, Kunming Medical University), Kunming, Yunnan 650118, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Pathology, Yunnan Cancer Hospital (The Third Affiliated Hospital, Kunming Medical University), Kunming, Yunnan 650118, P.R. China.
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Ran
authors.affiliation: Department of Abdominal Surgery, Yunnan Cancer Hospital (The Third Affiliated Hospital, Kunming Medical University), Kunming, Yunnan 650118, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D060888:Real-Time Polymerase Chain Reaction; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000378:metabolism*; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D005472:Fluorouracil