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A selective splicing variant of hepcidin mRNA in hepatocellular carcinoma cell lines.

Abstract：

:Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. By RT-PCR/agarose gel electrophoresis of hepcidin mRNA in a hepatocellular carcinoma cell line HLF, a smaller mRNA band was shown in addition to the wild-type hepcidin mRNA. From sequencing analysis, this additional band was a selective splicing variant of hepcidin mRNA lacking exon 2 of HAMP gene, producing the transcript that encodes truncated peptide lacking 20 amino acids at the middle of preprohepcidin. In the present study, we used the digital PCR, because such a small amount of variant mRNA was difficult to quantitate by the conventional RT-PCR amplification. Among seven hepatoma-derived cell lines, six cell lines have significant copy numbers of this variant mRNA, but not in one cell line. In the transient transfection analysis of variant-type hepcidin cDNA, truncated preprohepcidin has a different character comparing with native preprohepcidin: its product is insensitive to digestion, and secreted into the medium as a whole preprohepcidin form without maturation. Loss or reduction of function of HAMP gene by aberrantly splicing may be a suitable phenomenon to obtain the proliferating advantage of hepatoma cells.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Toki Y,Sasaki K,Tanaka H,Yamamoto M,Hatayama M,Ito S,Ikuta K,Shindo M,Hasebe T,Nakajima S,Sawada K,Fujiya M,Torimoto Y,Ohtake T,Kohgo Y

doi

10.1016/j.bbrc.2016.05.153

subject

Has Abstract

pub_date

2016-08-05 00:00:00

pages

501-507

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(16)30903-2

journal_volume

476

pub_type

杂志文章

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