Mechanism and function of decreased FOXO1 in renal cell carcinoma.
OBJECTIVE
Forkhead box O-class 1 (FOXO1), a putative tumor suppressor, is dysregulated in many cancers. Our study aims to reveal the underlying functions and regulation mechanisms of FOXO1 in renal cell carcinoma (RCC).


METHODS
The clinical significance of FOXO1 expression in surgically resected specimens was assessed by immunohistochemistry. The siRNAs targeted FOXO1 and miR-27a inhibitor were transfected into RCC cells. QRT-PCR, Western blot, and cell proliferation assay were used to assess the expression and function of FOXO1 and miR-27a.


RESULTS
The positive immunostaining for FOXO1 was low in 51 RCC samples compared with 15 normal kidney tissues. And the expression of FOXO1 was related with RCC subtypes and the grade and stage in clear cell RCC (cRCC) (P < 0.05). Inhibition of FOXO1 promoted proliferation of 769-P cells. However, upregulation of FOXO1 by miR-27a inhibitor was accompanied by the anti-proliferative effect in cells of 786-O and Caki-1. Furthermore, the expression of FOXO1 mRNA and miR-27a had inverse relation in eight cRCC samples.


CONCLUSIONS
Reduced expression of FOXO1 is common in RCC and a potentially suitable marker of different histological subtypes and prognosis of cRCC. Increasing expression of FOXO1 by the miR-27a inhibitor could prevent cell growth.
Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China.
Libin
L
Zhou
Bingde
B
Yin
Yongchao
Y
Liu
Yan
Y
Hong
Changcun
C
Zhang
Jie
J
Fan
D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000502:physiology; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering