Transcriptional repression of FOXO1 by KLF4 contributes to glioma progression.
In this study, our findings indicated that FOXO1 expression frequently decreased in glioma tissues and cells. FOXO1 expression decrease correlated with glioma progression and predicted a worse overall survival of glioma patients. Restored FOXO1 expression inhibited glioma cells invasion and suppressed glioma cells proliferation in vitro and growth in vivo. Additionally, we found that KLF4 expression frequently increased in glioma tissues and negatively correlated with FOXO1 expression. Bioinformatics analysis and experimental results indicated that KLF4 transcriptionally repressed FOXO1 expression in glioma cells. Moreover, KLF4 expression increase correlated with glioma progression and predicted a poorer overall survival of glioma patients. KLF4 knockdown attenuated glioma cells invasion and growth. These data provide a rationale for targeted intervention on KLF4-FOXO1 signaling pathway to suppress glioma progression.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Guodong
G
Tang
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.|The Institute of Skull Base Surgery and Neurooncology at Hunan Province, Changsha 410008, Hunan, China.
Dingyang
D
Liu
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Gelei
G
Xiao
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.|The Institute of Skull Base Surgery and Neurooncology at Hunan Province, Changsha 410008, Hunan, China.
Qing
Q
Liu
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.|The Institute of Skull Base Surgery and Neurooncology at Hunan Province, Changsha 410008, Hunan, China.
Jian
J
Yuan
D000328:Adult; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D015536:Down-Regulation; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D047368:Tumor Burden
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors
FOXO1; KLF4; glioma; progression; transcriptional regulation