title: Suppressor of Ty homolog-5, a novel tumor-specific human telomerase reverse transcriptase promoter-binding protein and activator in colon cancer cells.
abstract: The human telomerase reverse transcriptase (hTERT) promoter promotes differential hTERT gene expression in tumor cells and normal cells. However, information on the mechanisms underlying the differential hTERT transcription and induction of telomerase activity in tumor cells is limited. In the present study, suppressor of Ty homolog-5 (SPT5), a protein encoded by the SUPT5H gene, was identified as a novel tumor-specific hTERT promoter-binding protein and activator in colon cancer cells. We verified the tumor-specific binding activity of SPT5 to the hTERT promoter in vitro and in vivo and detected high expression levels of SUPT5H in colorectal cancer cell lines and primary human colorectal cancer tissues. SUPT5H was more highly expressed in colorectal cancer cases with distant metastasis than in cases without distant metastasis. Inhibition of endogenous SUPT5H expression by SUPT5H gene-specific short hairpin RNAs effectively attenuated hTERT promoter-driven green fluorescent protein (GFP) expression, whereas no detectable effects on CMV promoter-driven GFP expression in the same cells were observed. In addition, inhibition of SUPT5H expression not only effectively repressed telomerase activity, accelerated telomere shortening, and promoted cell senescence in colon cancer cells, but also suppressed cancer cell growth and migration. Our results demonstrated that SPT5 contributes to the up-regulation of hTERT expression and tumor development, and SUPT5H may potentially be used as a novel tumor biomarker and/or cancer therapeutic target.
authors.affiliation: Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.|Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Chao
authors.initials: C
authors.lastname: He
authors.affiliation: Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Hu
mesh_terms: D000368:Aged; D017209:Apoptosis; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D016922:Cellular Senescence; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D059505:Telomere Homeostasis; D013997:Time Factors; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D012333:RNA, Messenger; C112224:SUPT5H protein, human; D035602:Transcriptional Elongation Factors; C509186:TERT protein, human; D019098:Telomerase
keywords: SPT5; SUPT5H; colon cancer; promoter; telomerase activity