A selective splicing variant of hepcidin mRNA in hepatocellular carcinoma cell lines
Autor: | Koji Sawada, Katsuya Ikuta, Motohiro Shindo, Yasumichi Toki, Yutaka Kohgo, Takaaki Ohtake, Takumu Hasebe, Shunsuke Nakajima, Katsunori Sasaki, Hiroki Tanaka, Satoshi Ito, Yoshihiro Torimoto, Masayo Yamamoto, Mikihiro Fujiya, Mayumi Hatayama |
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Jazyk: | angličtina |
Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Hepatocellular carcinoma Ferroportin Biophysics Biology Aberrant splicing Biochemistry Intestinal absorption 03 medical and health sciences Exon 0302 clinical medicine Hepcidins Hepcidin Cell Line Tumor Humans Protein Isoforms Amino Acid Sequence RNA Messenger RNA Neoplasm Hepcidin mRNA Molecular Biology Gene Messenger RNA Base Sequence HAMP gene Liver Neoplasms Cell Biology Exons Molecular biology Alternative Splicing 030104 developmental biology HEK293 Cells 030220 oncology & carcinogenesis RNA splicing biology.protein Cell lines HAMP |
Zdroj: | Biochemical and Biophysical Research Communications. (4):501-507 |
ISSN: | 0006-291X |
DOI: | 10.1016/j.bbrc.2016.05.153 |
Popis: | Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 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. |
Databáze: | OpenAIRE |
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