Oncotarget

Research Papers:

Impact of microRNA-34a and polymorphism of its target gene CA9 on susceptibility to uterine cervical cancer

Shun-Fa Yang, Yu-Fan Liu, Chao-Wen Cheng, Wei-En Yang, Wea-Lung Lin, Jiunn-Liang Ko and Po-Hui Wang _

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Oncotarget. 2017; 8:77860-77871. https://doi.org/10.18632/oncotarget.20842

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Abstract

Shun-Fa Yang1,2, Yu-Fan Liu3, Chao-Wen Cheng4, Wei-En Yang1,2, Wea-Lung Lin5,6, Jiunn-Liang Ko1,2 and Po-Hui Wang1,5,7

1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

2Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

3Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan

4Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

5School of Medicine, Chung Shan Medical University, Taichung, Taiwan

6Department of Pathology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung, Taiwan

7Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan

Correspondence to:

Po-Hui Wang, email: [email protected]

Keywords: carbonic anhydrase, single nucleotide polymorphisms, miR-34a, migration, tissue microarray

Received: April 18, 2017    Accepted: August 17, 2017    Published: September 12, 2017

ABSTRACT

The purposes of this study were to associate the genetic polymorphisms in carbonic anhydrase (CA) 9 with uterine cervical cancer and identify the clinical implications. Three single-nucleotide polymorphisms (SNPs), rs2071676 (+201, G/A), rs3829078 (+1081, A/G), and rs1048638 (+1584, C/A), and an 18-base-pair deletion/insertion (376del393) in CA9 were examined. We used the Boyden chamber assay to evaluate the influence of CA9 on the migration of cervical cancers. Tissue microarrays were used to evaluate CAIX immunoreactivity and determine its clinical significance. The results revealed that the CA9 SNP rs1048638 is the only significant polymorphism that increases the risk of cervical cancer in Taiwanese women. We discovered that the CA9 SNP rs1048638 influences the expression of CA9 through the interaction between the 3′-untranslated region (UTR) of exon 11, where the SNP is located, and miR-34a, and influences the migration of cervical cancer cells. Moreover, we demonstrated that CAIX immunoreactivity is related to the occurrence of cervical cancer, and elevated CAIX immunoreactivity is associated with a more advanced stage. In conclusion, the finding that the CA9 SNP rs1048638 exerts its action through duplexes of the miR-34a and CA9 3′-UTRs and plays a vital role in cervical cancer in Taiwanese women may be applicable to translational medicine.


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