NIRF is frequently upregulated in colorectal cancer and its oncogenicity can be suppressed by let-7a microRNA.
Np95 ICBP90 RING finger (NIRF) is essential for the regulation of cell proliferation and has been implicated in tumorigenesis. However, the role of NIRF in colorectal cancer (CRC) remains unclear. In this study, we demonstrated that NIRF expression was aberrantly increased in CRC tissues and associated with poor overall survival. Bioinformatics analysis indicated that NIRF was a putative target of the microRNA let-7a, which was confirmed by luciferase reporter assay. We then demonstrated in vitro that enforced expression of let-7a, or knockdown of NIRF, led to reduced CRC cell proliferation due to cell cycle arrest at the G0/G1 phase and reduced cell migration. Finally, an in vivo tumorigenicity assay in nude mice showed that synthetic let-7a suppressed NIRF expression and reduced tumor growth. Taken together, our results provide new evidence that NIRF has an oncogenic role in CRC. This opens up the possibility of targeting NIRF and let-7a for CRC therapy.
Department of Surgery, Sixth People's Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, China.
Feng
F
Wang
Peng
P
Zhang
Yanlei
Y
Ma
Jianjun
J
Yang
Mary Pat
MP
Moyer
Chenzhang
C
Shi
Jiayuan
J
Peng
Huanlong
H
Qin
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D020413:3' Untranslated Regions; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; C465619:UHRF2 protein, human; D044767:Ubiquitin-Protein Ligases