The impact of miR-34a on protein output in hepatocellular carcinoma HepG2 cells.
MicroRNAs are small non-coding RNA molecules that play essential roles in biological processes ranging from cell cycle to cell migration and invasion. Accumulating evidence suggests that miR-34a, as a key mediator of p53 tumor suppression, is aberrantly expressed in human cancers. In the present study, we aimed to explore the precise biological role of miR-34a and the global protein changes in HCC cell line HepG2 cells transiently transfected with miR-34a. Transfection of miR-34a into HepG2 cells caused suppression of cell proliferation, inhibition of cell migration and invasion. It also induced an accumulation of HepG2 cells in G1 phase. Among 116 protein spots with differential expression separated by 2-DE method, 34 proteins were successfully identified by MALDI-TOF/TOF analysis. Of these, 15 downregulated proteins may be downstream targets of miR-34a. Bioinformatics analysis produced a protein-protein interaction network, which revealed that the p53 signaling pathway and cell cycle pathway were two major hubs containing most of the proteins regulated by miR-34a. Cytoskeletal proteins such as LMNA, GFAP, MACF1, ALDH2, and LOC100129335 are potential targets of miR-34a. In conclusion, abrogation of miR-34a function could cause downstream molecules to switch on or off, leading to HCC development.
Cheng
Jun
J
Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, PR China.
Zhou
Lin
L
Xie
Qin-Fen
QF
Xie
Hai-Yang
HY
Wei
Xu-Yong
XY
Gao
Feng
F
Xing
Chun-Yang
CY
Xu
Xiao
X
Li
Lan-Juan
LJ
Zheng
Shu-Sen
SS
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D020543:Proteome / Q000032:analysis*; D017422:Sequence Analysis, DNA
C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D020543:Proteome