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瘦素和瘦素受体在口腔鳞状细胞中的致癌作用研究

A study on oncogenic role of leptin and leptin receptor in oral squamous cell.

作者信息

Hussain Syed Rizwan, Naqvi Hena, Gupta Shalini, Mahdi Abbas Ali, Kumari Pratibha, Waseem Mohammad, Ahmad Mohammad Kaleem

机构信息

Molecular Cell Biology Lab, Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, 226 003, India.

出版信息

Tumour Biol. 2015 Aug;36(8):6515-23. doi: 10.1007/s13277-015-3342-1. Epub 2015 Mar 26.

Abstract

Leptin been mainly produced by adipose tissue and cancer cells is the most studied adipokine, amongst the several cytokines. Leptin is an antiapoptotic molecule and inducer of cancer stem cells as well as activates cell proliferation. Its oncogenic, mitogenic, proinflammatory and proangiogenic actions lead to its vital roles in tumourigenesis. Two common functional DNA polymorphisms in the genes of leptin G2548A (LEP) and leptin receptor A668G (LEPR) affect the amount of circulating cytokine-type hormone leptin with risk for development of oral squamous cell carcinoma (OSCC). The present study investigated whether these LEP and LEPR gene polymorphisms are affecting risk for OSCC by comparing the genotypes of patients with controls. A total of 306 OSCC and 228 controls participated in this study. We have determined the frequency of LEP (G2548A) and LEPR (A668G) gene polymorphisms in OSCC cases and controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The incidence of leptin gene G2548A homozygous mutant AA polymorphism was significantly increased in the OSCC patients (p = 0.002, odds ratio (OR) = 2.4, 95 % confidence interval (CI) = 1.37-4.22) when compared with controls, and leptin receptor A668G homozygous mutant GG polymorphism was significantly high in the OSCC patients as compared to controls (p = 0.000, OR = 3.8, 95 % CI = 1.98-7.62). The polymorphism of homozygous mutant allele A of leptin gene and G allele of leptin receptor may be associated with increased risk for OSCC. The observations showed regular increase of supporting role of leptin in OSCC. The present study showed an association of AA genotype and A allele of LEP G2548A as well as GG genotype and G allele of LEPR A668G polymorphisms with increased risk for OSCC in north Indian patients. Moreover, the combination of both the polymorphisms may be involved in susceptibility and progression of OSCC.

摘要

瘦素主要由脂肪组织和癌细胞产生,是几种细胞因子中研究最多的脂肪因子。瘦素是一种抗凋亡分子和癌症干细胞诱导剂,还能激活细胞增殖。其致癌、促有丝分裂、促炎和促血管生成作用使其在肿瘤发生中发挥重要作用。瘦素基因G2548A(LEP)和瘦素受体A668G(LEPR)基因中的两种常见功能性DNA多态性会影响循环细胞因子型激素瘦素的量,与口腔鳞状细胞癌(OSCC)的发生风险相关。本研究通过比较患者与对照组的基因型,调查这些LEP和LEPR基因多态性是否会影响OSCC的风险。共有306例OSCC患者和228名对照参与了本研究。我们通过聚合酶链反应和限制性片段长度多态性(PCR-RFLP)确定了OSCC病例和对照中LEP(G2548A)和LEPR(A668G)基因多态性的频率。与对照组相比,OSCC患者中瘦素基因G2548A纯合突变体AA多态性的发生率显著增加(p = 0.002,优势比(OR)= 2.4,95%置信区间(CI)= 1.37 - 4.22),与对照组相比,OSCC患者中瘦素受体A668G纯合突变体GG多态性显著更高(p = 0.000,OR = 3.8,95%CI = 1.98 - 7.62)。瘦素基因纯合突变等位基因A和瘦素受体G等位基因的多态性可能与OSCC风险增加有关。观察结果表明瘦素在OSCC中的支持作用呈规律性增加。本研究表明,在印度北部患者中,LEP G2548A的AA基因型和A等位基因以及LEPR A668G多态性的GG基因型和G等位基因与OSCC风险增加相关。此外,两种多态性的组合可能与OSCC的易感性和进展有关。

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