title: Dysregulation of metallothionein and circadian genes in human hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is the major threat to human health, and disruption of circadian clock genes is implicated in hepatocarcinogenesis. This study examined the dysregulation of metallothioneins and circadian genes in achieved human HCC (n = 24), peri-HCC tissues (n = 24) as compared with normal human livers (n = 36). Total RNA was extracted and reverse transcribed. Real-time RT-qPCR was performed to determine the expression of genes of interest. The results demonstrated the downregulation of metallothionein-1 (MT-1), MT-2, and metal transcription factor-1 (MFT-1) in human HCC as compared with Peri-HCC and normal tissues. MTs are a biomarker for HCC and have typical circadian rhythms; the expression of major circadian clock genes was also determined. HCC produced a dramatic decrease in the expression of core clock genes, circadian locomotor output cycles kaput (Clock) and brain and muscle Arnt-like protein 1 (Bmal1), and decreased the expression of the clock feedback control genes, Periods (Per1, Per2) and Cryptochromes (Cry1, Cry2). On the other hand, the expression of clock target genes nuclear orphan receptor factor protein (Nr1d1) and D-box-binding protein (Dbp) was upregulated as compared with Peri-HCC and normal livers. Peri-HCC also had mild alterations in these gene expressions. In summary, the present study clearly demonstrated the dysregulation of MTs and circadian clock genes in human HCC, which could provide the information of targeting MT and circadian clock in HCC management.
authors.affiliation: a Key Lab for Basic Pharmacology of Ministry of Education , Zunyi Medical College , Zunyi , China.
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.affiliation: a Key Lab for Basic Pharmacology of Ministry of Education , Zunyi Medical College , Zunyi , China.
authors.forename: Yuan-Fu
authors.initials: YF
authors.lastname: Lu
authors.affiliation: b The Institute of Organ Transplantation , The General Hospital of Chinese People's Armed Police Forces , Beijing , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: a Key Lab for Basic Pharmacology of Ministry of Education , Zunyi Medical College , Zunyi , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D056926:CLOCK Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes / Q000378:metabolism; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D014408:Biomarkers, Tumor; C538963:CRY1 protein, human; C538966:CRY2 protein, human; D056931:Cryptochromes; C530099:MT1A protein, human; C491053:MT2A protein, human; D026901:Membrane Transport Proteins; C539022:PER1 protein, human; C421902:PER2 protein, human; D056950:Period Circadian Proteins; C417506:SLC25A32 protein, human; D012313:RNA; D008668:Metallothionein; D056926:CLOCK Proteins; C538943:CLOCK protein, human
keywords: Bmal1; Dbp; Nr1d1; clock; hepatocellular carcinoma; meltallothionein