title: Attenuation of krüppel-like factor 4 facilitates carcinogenesis by inducing g1/s phase arrest in clear cell renal cell carcinoma.
abstract: Krüppel-like factor 4 (KLF4) is a transcription factor with diverse functions in various cancer types; however, the function of KLF4 in clear cell renal cell carcinoma (ccRCC) carcinogenesis remains unknown. In this study, we initially examined KLF4 expression by using a cohort of surgically removed ccRCC specimens and cell lines. Results indicated that the transcription and translation of KLF4 were lower in ccRCC tissues than in patient-matched normal tissues. Furthermore, the KLF4 expression was significantly downregulated in the five ccRCC cell lines at protein and mRNA levels compared with that in normal renal proximal tubular epithelial cell lines (HKC). KLF4 downregulation was significantly correlated with tumor stage and tumor diameter. Promoter hypermethylation may contribute to its low expression. In addition, in vitro studies indicated that the KLF4 overexpression significantly inhibited proliferation in human ccRCC cell lines 786-O and ACHN. Moreover, the KLF4 overexpression arrested the cell cycle progress at the G1/S phase transition by upregulating p21 (WAF1/CIP1) expression and downregulating cyclin D1 expression, KLF4 knockdown in HKC cells did the opposite. In vivo studies confirmed the anti-proliferative effect of KLF4. Our results suggested that KLF4 had an important function in suppressing the growth of ccRCC.
authors.affiliation: Department of Urology/State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Medical School of Chinese PLA, Beijing, China.
authors.forename: Erlin
authors.initials: E
authors.lastname: Song
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Hongzhao
authors.initials: H
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Ni
authors.forename: Weihao
authors.initials: W
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Yang
authors.initials: Y
authors.lastname: Fan
authors.forename: Haigang
authors.initials: H
authors.lastname: Pang
authors.forename: Taoping
authors.initials: T
authors.lastname: Shi
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Baojun
authors.initials: B
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D059807:S Phase Cell Cycle Checkpoints; D047368:Tumor Burden
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D019938:Cyclin D1