YY1-C/EBPα-miR34a regulatory circuitry is involved in renal cell carcinoma progression.
Renal cell carcinoma (RCC) is a common urological malignancy. It remains unclear, however, whether Yin Yang 1 (YY1) plays a functional role in the development of human RCC. In the present study, we demonstrated that levels of YY1 were significantly increased in primary RCC tissues when compared to these levels in the matched healthy tissues. YY1 knockdown inhibited cell growth, migration and invasion of RCC cells. Additionally, we highlighted a positive feedback-loop pathway resulting in YY1 upregulation. We observed that overexpression of YY1 caused repression of C/EBPα and the inhibition of C/EBPα led to the suppression of miR-34a. Since YY1 is a direct target of miR-34a, the low level of miR-34a increased the expression of YY1, promoting the aggressiveness of RCC cells. Furthermore, this feedforward mechanism was found in RCC tissues. We observed that miR-34a was downregulated in the pools of cancer tissues when compared to that of the normal tissues. The expression of miR-34a displayed an inverse correlation with YY1, but a positive correlation with C/EBPα. In conclusion, our study highlights the importance of a novel regulatory circuitry for YY1 activation in maintaining the aggressive phenotypes of RCC.
Department of Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
Wenhao
W
Weng
Department of Laboratory Medicine, Shanghai Putuo District Central Hospital, Shanghai 200013, P.R. China.
Minli
M
Wang
Department of Laboratory Medicine, Shanghai Yangpu District Central Hospital, Shanghai 200090, P.R. China.
Suhong
S
Xie
Department of Laboratory Medicine, Shanghai Yangpu District Central Hospital, Shanghai 200090, P.R. China.
Yin
Y
Long
Department of Laboratory Medicine, Shanghai Yangpu District Central Hospital, Shanghai 200090, P.R. China.
Feng
F
Li
Department of Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
Fenyong
F
Sun
Department of Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
Yongchun
Y
Yu
Department of Laboratory Medicine, Shanghai Yangpu District Central Hospital, Shanghai 200090, P.R. China.
Zhi
Z
Li
D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D022763:CCAAT-Enhancer-Binding Protein-alpha; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D050986:YY1 Transcription Factor; C494698:YY1 protein, human