PDF(Pubmed)
Abstract：
The disease burden of Oral Squamous Cell Carcinoma (OSCC) is rising day-by-day and is expected to rise 62 % through 2035. The chewing of tobacco, areca nut, and betel leaf, poor oral hygiene, and chronic infection are common risk factors of OSCC, but genetic and epigenetic factors also contribute equally. MicroRNAs (miRNAs) are comprised of small, non-coding endogenous RNA that regulate a plethora of biological activities by targeting messenger RNA through degradation or inhibition. Single Nucleotide Polymorphisms (SNPs) in miRNA genes can regulate the development and progression of OSCC. The present study aimed to determine the association between SNPs in miRNA genes (miRSNPs) with the risk of OSCC. A case-control study involving 225 histo-pathologically confirmed OSCC cases and 225 healthy controls was conducted, where 25 miRSNPs were analyzed by iPLEX MassArray analysis. A SNP rs12220909 in MIR4293 showed a highly protective effect (CC vs GG, OR = 0.0431, 95%CI = 0.005-0.323, p = 3e-6). Whereas three SNPs, namely, rs4705342 in MIR143 (CC vs TT, OR = 2.25, 95%CI = 2.00-2.53, p = 0.0008), rs531564 in MIR124 (CC vs GG, OR = 24.18, 95%CI = 3.22-181.37, p = 3e-6), and rs3746444 in MIR499 (AA vs GG, OR = 2.01, 95%CI = 1.32-3.05, p = 0.001) were significantly associated with a higher risk of OSCC. Additionally, NanoString-based nCounter miRNA expression profiling revealed that miR-499a (Log2FC = -1.07), and miR-143 (Log2FC = -1.56) were aberrantly expressed in OSCC tissue. Taken together, the above miSNPs may contribute to the high incidence of OSCC in central India. However, further studies with large cohorts and ethnic stratification are required to validate our findings.
摘要：
口腔鳞状细胞癌（OSCC）的疾病负担日益增加，预计到2035年将增加62％。烟草的咀嚼，槟榔,还有槟榔叶,口腔卫生差，慢性感染是OSCC的常见危险因素，但是遗传和表观遗传因素也有同样的作用。microRNAs（miRNAs）是由小的，非编码内源性RNA，通过降解或抑制靶向信使RNA来调节过多的生物活性。miRNA基因中的单核苷酸多态性(SNPs)可以调控OSCC的发生发展。本研究旨在确定miRNA基因中的SNP（miRSNP）与OSCC风险之间的关联。对225例经病理证实的OSCC病例和225例健康对照进行病例对照研究,其中通过iPLEXMassArray分析分析25个miRSNP。MIR4293中的SNPrs12220909显示出高度的保护作用(CCvsGG，OR=0.0431，95CI=0.005-0.323，p=3e-6）。而三个SNP，即,MIR143中的rs4705342(CCvsTT,OR=2.25，95CI=2.00-2.53，p=0.0008），MIR124中的rs531564（CC与GG，OR=24.18，95CI=3.22-181.37，p=3e-6），和MIR499中的rs3746444（AA与GG，OR=2.01，95CI=1.32-3.05，p=0.001）与OSCC的高风险显着相关。此外,基于NanoString的nCountermiRNA表达谱显示miR-499a(Log2FC=-1.07),miR-143(Log2FC=-1.56)在OSCC组织中异常表达。一起来看,上述miSNPs可能导致印度中部OSCC的高发.然而,我们需要对大型队列和种族分层进行进一步研究以验证我们的发现.
