3′UTR polymorphisms of carbonic anhydrase IX determine the miR-34a targeting efficiency and prognosis of hepatocellular carcinoma

Kuo Tai Hua, Yu Fan Liu, Chia Lang Hsu, Tsu Yao Cheng, Ching Yao Yang, Jeng Shou Chang, Wei Jiunn Lee, Michael Hsiao, Hsueh Fen Juan, Ming Hsien Chien, Shun Fa Yang

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Abstract

Carbonic anhydrase IX (CA9) expression level has been considered as a poor prognostic factor in hepatocellular carcinoma (HCC) patients. However, the judging criteria of CA9 level is hard to define for potential clinical applications. Unlike CA9 expression level, CA9 polymorphism is poorly documented in HCC. Here, we found that people carry A allele at CA9 rs1048638, a 3′UTR SNP, has higher risk of HCC. rs1048638-CA correlates with advanced stages, larger tumor sizes, more vascular invasion, and shorter survival of HCC patients. A allele at CA9 rs1048638 impairs miR-34a, a tumor suppressor miRNA in HCC, binding to CA9 3′UTR and desensitizes CA9 mRNA to miR-34a-dependent RNA degradation. CA9 expression levels were also correlated with miR-34a levels and rs1048638 genotypes in HCC patients. rs1048638 influences HCC risk and progression through effects on miR-34a-targeted CA9 expression in HCC. In conclusion, genetic variations of the CA9 3′UTR play important roles in regulating CA9 expression and cancer progression, which is a novel determinant and target for HCC metastasis and prognosis.

Original languageEnglish
Article number4466
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Hepatocellular Carcinoma
Alleles
Carbonic Anhydrase IX
Neoplasms
RNA Stability
MicroRNAs
Single Nucleotide Polymorphism
Blood Vessels
Genotype
Neoplasm Metastasis
Messenger RNA
Survival

ASJC Scopus subject areas

  • General

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3′UTR polymorphisms of carbonic anhydrase IX determine the miR-34a targeting efficiency and prognosis of hepatocellular carcinoma. / Hua, Kuo Tai; Liu, Yu Fan; Hsu, Chia Lang; Cheng, Tsu Yao; Yang, Ching Yao; Chang, Jeng Shou; Lee, Wei Jiunn; Hsiao, Michael; Juan, Hsueh Fen; Chien, Ming Hsien; Yang, Shun Fa.

In: Scientific Reports, Vol. 7, No. 1, 4466, 01.12.2017.

Research output: Contribution to journalArticle

Hua, Kuo Tai ; Liu, Yu Fan ; Hsu, Chia Lang ; Cheng, Tsu Yao ; Yang, Ching Yao ; Chang, Jeng Shou ; Lee, Wei Jiunn ; Hsiao, Michael ; Juan, Hsueh Fen ; Chien, Ming Hsien ; Yang, Shun Fa. / 3′UTR polymorphisms of carbonic anhydrase IX determine the miR-34a targeting efficiency and prognosis of hepatocellular carcinoma. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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abstract = "Carbonic anhydrase IX (CA9) expression level has been considered as a poor prognostic factor in hepatocellular carcinoma (HCC) patients. However, the judging criteria of CA9 level is hard to define for potential clinical applications. Unlike CA9 expression level, CA9 polymorphism is poorly documented in HCC. Here, we found that people carry A allele at CA9 rs1048638, a 3′UTR SNP, has higher risk of HCC. rs1048638-CA correlates with advanced stages, larger tumor sizes, more vascular invasion, and shorter survival of HCC patients. A allele at CA9 rs1048638 impairs miR-34a, a tumor suppressor miRNA in HCC, binding to CA9 3′UTR and desensitizes CA9 mRNA to miR-34a-dependent RNA degradation. CA9 expression levels were also correlated with miR-34a levels and rs1048638 genotypes in HCC patients. rs1048638 influences HCC risk and progression through effects on miR-34a-targeted CA9 expression in HCC. In conclusion, genetic variations of the CA9 3′UTR play important roles in regulating CA9 expression and cancer progression, which is a novel determinant and target for HCC metastasis and prognosis.",
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AU - Yang, Ching Yao

AU - Chang, Jeng Shou

AU - Lee, Wei Jiunn

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AU - Juan, Hsueh Fen

AU - Chien, Ming Hsien

AU - Yang, Shun Fa

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