Tiwari Shikha, Pandey Ritu, Kumar Vinay, Das Saikat, Gupta Vikas, Nema Rajeev, Kumar Ashok
Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Bhopal, Saket Nagar, Bhopal 462020, India.
Department of Biotechnology and Bioengineering, Institute of Advanced Research, Gandhinagar, Gujarat, India.
Noncoding RNA Res. 2024 Jul 14;9(4):1333-1341. doi: 10.1016/j.ncrna.2024.07.002. eCollection 2024 Dec.
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 showed a highly protective effect ( OR = 0.0431, 95%CI = 0.005-0.323, p = 3e-6). Whereas three SNPs namely, rs4705342 in (, OR = 2.25, 95%CI = 2.00-2.53, p = 0.0008), rs531564 in (, OR = 24.18, 95%CI = 3.22-181.37, p = 3e-6), and rs3746444 in MIR499 (, 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.
口腔鳞状细胞癌（OSCC）的疾病负担日益加重，预计到2035年将上升62%。咀嚼烟草、槟榔和蒌叶、口腔卫生差以及慢性感染是OSCC的常见风险因素，但遗传和表观遗传因素也同样起作用。微小RNA（miRNA）由小的非编码内源性RNA组成，通过降解或抑制靶向信使RNA来调节大量生物活性。miRNA基因中的单核苷酸多态性（SNP）可调节OSCC的发生和发展。本研究旨在确定miRNA基因中的SNP（miRSNP）与OSCC风险之间的关联。进行了一项病例对照研究，纳入225例经组织病理学确诊的OSCC病例和225例健康对照，通过iPLEX MassArray分析对25个miRSNP进行检测。 中的一个SNP rs12220909显示出高度保护作用（OR = 0.0431，95%CI = 0.005 - 0.323，p = 3e - 6）。而三个SNP，即 中的rs4705342（ ，OR = 2.25，95%CI = 2.00 - 2.53，p = 0.0008）、 中的rs531564（ ，OR = 24.18，95%CI = 3.22 - 181.37，p = 3e - 6）以及MIR499中的rs3746444（ ，OR = 2.01，95%CI = 1.32 - 3.05，p = 0.001）与OSCC的较高风险显著相关。此外，基于NanoString的nCounter miRNA表达谱分析显示，miR - 499a（Log2FC = -1.07）和miR - 143（Log2FC = -1.56）在OSCC组织中异常表达。综上所述，上述miSNP可能是印度中部OSCC高发的原因之一。然而，需要进一步进行大规模队列研究和种族分层研究来验证我们的发现。
