Screening of differential microRNA and prediction of target genes between human immunodeficiency virus-Burkitt lymphoma and diffuse large B cell lymphoma

Di Wang, Dong Zeng, Ye Zheng, Peng Zhang, Yan-ling Feng
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Abstract

Objective To screen the differential microRNA (miRNA) in human immunodeficiency virus (HIV) related Burkitt lymphoma (BL) and diffuse large B cell lymphoma (DLBCL). Methods Five freshly frozen tissue samples of BL and 3 freshly frozen tissu samples of DLBCL, 19 paraffin specimens of BL and 15 paraffin specimens of DLBCL were collected from Shanghai Public Health Clinical Center. Agilent human miRNA microarrays were employed to detect the miRNA expressions in fresh frozen BL tissues and fresh frozen DLBCL tissues, and to find out differential miRNA. SmartRNAplex™ miRNA was employed to verify the expressions of crucial miRNA in BL formalin fixed and paraffin-embedded tissues and DLBCL FFPET. Bioinformatics methods were used to predict the target genes of the crucial miRNA. Results Compared with DLBCL group, 42 differential miRNA were detected in BL group. Among them, 28 miRNA were up-regulated and 14 miRNA were down-regulated in BL group. According to positive control in eukaryote and high-expression molecular contributing to the emergence of tumor, 5 crucial miRNA were selected from 28 up-regulated miRNA in BL group for validation. The result was consistent with that of Agilent human miRNA microarrays. Compared with the DLBCL group, 5 crucial miRNA were all up-regulated in BL, which were miRNA-16-2-3p, miRNA-20a-3p, miRNA-130b-3p, miRNA-185-5p and miRNA-423-5p (t=2.7151, 2.539, 2.750, 4.004, and 3.625, respectively, all P<0.05). The corresponding target genes of miRNA-16-2-3p might be CTNND2 and RAD21.The target genes of miRNA-20a-3p might mainly be DYRK1A and GPAM. The target genes of miRNA-130b-3p might mainly be IRF1, DICER1 and PTEN. The target genes of miRNA-185-5p might mainly be VEGFA, NFATC3 and SEC24C.The target genes of miRNA-423-5p might mainly be PA2G4 and PNKD. Conclusions There are significantly differentially expressed miRNA between BL and DLBCL tissues. These miRNA are expected to provide new molecular markers for diagnosis and differential diagnosis of BL and DLBCL. Potential target genes of crucial miRNA are related with cell survival, proliferation, differentiation, apoptosis and carcinogenesis, etc, which may play important roles in the origination and progress of BL. Key words: Human immunodeficiency virus; Burkitt lymphoma; Lymphoma, large B-cell, diffuse; MicroRNA; Clinical pathology
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人免疫缺陷病毒-伯基特淋巴瘤与弥漫性大B细胞淋巴瘤差异microRNA筛选及靶基因预测
目的筛选人类免疫缺陷病毒(HIV)相关的伯基特淋巴瘤(BL)和弥漫性大B细胞淋巴瘤(DLBCL)的差异性微小RNA(miRNA)。方法从上海市公共卫生临床中心采集5份BL新鲜冷冻组织标本和3份DLBCL新鲜冷冻组织样本,19份BL石蜡标本和15份DLBCL石蜡标本。采用安捷伦人miRNA微阵列检测新鲜冷冻BL组织和新鲜冷冻DLBCL组织中miRNA的表达,并找出差异miRNA。SmartRNAplex™ miRNA用于验证关键miRNA在BL福尔马林固定和石蜡包埋组织以及DLBCL-FFPET中的表达。生物信息学方法用于预测关键miRNA的靶基因。结果BL组与DLBCL组相比,共检测到42个不同的miRNA。其中BL组有28个miRNA上调,14个miRNA下调。根据真核生物中的阳性对照和对肿瘤发生有贡献的高表达分子,从BL组的28个上调的miRNA中选出5个关键miRNA进行验证。该结果与安捷伦人类miRNA微阵列的结果一致。与DLBCL组相比,BL中有5个关键的miRNA均上调,分别是miRNA-16-2-3p、miRNA-20a-3p、iRNA-130b-3p、miRNA-185-5p和miRNA-423-5p(t=2.7151、2.539、2.750、4.004和3.625,均P<0.05)。miRNA-16-2-3p的相应靶基因可能是CTNND2和RAD21。miRNA-20a-1p的靶基因可能主要是DYRK1A和GPAM。miRNA-130b-3p的靶基因可能主要是IRF1、DICER1和PTEN。miRNA-185-5p的靶基因可能主要是VEGFA、NFATC3和SEC24C。miRNA-423-5p的靶蛋白可能主要是PA2G4和PNKD。结论BL和DLBCL组织中存在显著差异表达的miRNA。这些miRNA有望为BL和DLBCL的诊断和鉴别诊断提供新的分子标记。关键miRNA的潜在靶基因与细胞存活、增殖、分化、凋亡和致癌等有关,可能在BL的起源和发展中发挥重要作用。关键词:人类免疫缺陷病毒;伯基特淋巴瘤;淋巴瘤,大B细胞,弥漫性;微小核糖核酸;临床病理学
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