[Down-regulation of PGC-1alpha expression in human hepatocellular carcinoma].
OBJECTIVE
To study the effect of PGC-1alpha in human liver carcinogenesis, and explore the regulatory role of PGC-1alpha in the development of liver cancer.


METHODS
The changes of PGC-1alpha mRNA level in normal human liver tissues and human liver tumors was examined by quantitative RT-PCR. PGC-1alpha mRNA level was interfered by siRNA in human liver cell line L02 in vitro, and their morphological changes were observed by pathology with HE staining. The ultrastructure of cells was observed by electron microscopy. In addition, the gene expression pattern of decreasing PGC-1alpha in L02 cells and liver tumor tissue was compared by human genome 70-mer oligonucleotide microarray analysis.


RESULTS
PGC-1alpha expression was weaker in the malignant liver tumors compared with that in normal liver tissues. When PGC-1alpha expression was suppressed in human liver L02 cells, the cells became smaller with enlarged nuclei, and myelin figures were observed in mitochondria by electron microscopy, similar with the ultrastructure of liver cancer cells. Microarray analysis showed that the decrease of PGC-1alpha in L02 cells induced up-regulation of some oncogenes and adhesive genes, and down-regulation of a number of tumor suppressor genes and cell proliferation suppressor genes. The changes of decreasing expression pattern of PGC-1alpha gene in L02 cells were similar to those in human liver cancer tissue.


CONCLUSIONS
The results of the present study show that PGC-1alpha is down-regulated in liver cancers and is involved in the malignant transformation in human normal liver cells in vitro, suggesting an important regulatory role of PGC-1alpha in the development of liver cancer.
Ba
Yi
Y
Department of Gastrointestinal Oncology, Cancer Insititute and Hospital, Tianjin Medical University, Tianjin 300060, China.
Zhang
Chun-ni
CN
Zhang
Yan
Y
Zhang
Chen-yu
CY
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors