Yang Shun-Fa, Liu Yu-Fan, Cheng Chao-Wen, Yang Wei-En, Lin Wea-Lung, Ko Jiunn-Liang, Wang Po-Hui
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
Oncotarget. 2017 Sep 12;8(44):77860-77871. doi: 10.18632/oncotarget.20842. eCollection 2017 Sep 29.
The purposes of this study were to associate the genetic polymorphisms in carbonic anhydrase 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 were examined. We used the Boyden chamber assay to evaluate the influence of on the migration of cervical cancers. Tissue microarrays were used to evaluate CAIX immunoreactivity and determine its clinical significance. The results revealed that the SNP rs1048638 is the only significant polymorphism that increases the risk of cervical cancer in Taiwanese women. We discovered that the SNP rs1048638 influences the expression of 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 SNP rs1048638 exerts its action through duplexes of the miR-34a and 3'-UTRs and plays a vital role in cervical cancer in Taiwanese women may be applicable to translational medicine.
本研究旨在探讨碳酸酐酶9基因多态性与子宫颈癌的关系,并确定其临床意义。研究检测了3个单核苷酸多态性(SNP),即rs2071676(+201,G/A)、rs3829078(+1081,A/G)和rs1048638(+1584,C/A),以及一个18碱基对的缺失/插入(376del393)。我们采用Boyden小室法评估其对子宫颈癌细胞迁移的影响。利用组织芯片评估CAIX免疫反应性并确定其临床意义。结果显示,SNP rs1048638是唯一显著增加台湾女性子宫颈癌风险的多态性。我们发现SNP rs1048638通过位于外显子11的3'非翻译区(UTR)与miR-34a之间的相互作用影响其表达,并影响子宫颈癌细胞的迁移。此外,我们证明CAIX免疫反应性与子宫颈癌的发生有关,CAIX免疫反应性升高与更晚期别相关。总之,SNP rs1048638通过miR-34a与3'-UTR的双链发挥作用,并在台湾女性子宫颈癌中起重要作用这一发现可能适用于转化医学。