Fawzy Manal S, Toraih Eman A, Ibrahiem Afaf, Abdeldayem Hala, Mohamed Amany O, Abdel-Daim Mohamed M
Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
PLoS One. 2017 Nov 1;12(11):e0187310. doi: 10.1371/journal.pone.0187310. eCollection 2017.
Previous reports have suggested the significant association of miRNAs aberrant expression with tumor initiation, progression and metastasis in cancer, including gastrointestinal (GI) cancers. The current preliminary study aimed to evaluate the relative expression levels of miR-196a2 and three of its selected apoptosis-related targets; ANXA1, DFFA and PDCD4 in a sample of GI cancer patients. Quantitative real-time PCR for miR-196a2 and its selected mRNA targets, as well as immunohistochemical assay for annexin A1 protein expression were detected in 58 tissues with different GI cancer samples. In addition, correlation with the clinicopathological features and in silico network analysis of the selected molecular markers were analyzed. Stratified analyses by cancer site revealed elevated levels of miR-196a2 and low expression of the selected target genes. Annexin protein expression was positively correlated with its gene expression profile. In colorectal cancer, miR-196a over-expression was negatively correlated with annexin A1 protein expression (r = -0.738, p < 0.001), and both were indicators of unfavorable prognosis in terms of poor differentiation, larger tumor size, and advanced clinical stage. Taken together, aberrant expression of miR-196a2 and the selected apoptosis-related biomarkers might be involved in GI cancer development and progression and could have potential diagnostic and prognostic roles in these types of cancer; particularly colorectal cancer, provided the results experimentally validated and confirmed in larger multi-center studies.
先前的报告表明，包括胃肠道（GI）癌症在内的癌症中，微小RNA（miRNA）异常表达与肿瘤的发生、发展和转移密切相关。当前的初步研究旨在评估miR-196a2及其选定的三个凋亡相关靶标的相对表达水平；即膜联蛋白A1（ANXA1）、DNA片段化因子α（DFFA）和程序性细胞死亡蛋白4（PDCD4）在一组胃肠道癌症患者样本中的表达情况。对58个不同胃肠道癌症样本的组织进行了miR-196a2及其选定的mRNA靶标的定量实时聚合酶链反应（PCR），以及膜联蛋白A1蛋白表达的免疫组织化学检测。此外，还分析了所选分子标志物与临床病理特征的相关性以及计算机网络分析结果。按癌症部位进行的分层分析显示，miR-196a2水平升高，选定的靶基因表达降低。膜联蛋白的蛋白表达与其基因表达谱呈正相关。在结直肠癌中，miR-196a过表达与膜联蛋白A1蛋白表达呈负相关（r = -0.738，p < 0.001），就分化差、肿瘤体积大及临床分期晚而言，二者均为预后不良的指标。综上所述，miR-196a2和选定的凋亡相关生物标志物的异常表达可能参与胃肠道癌症的发生和发展，并且在这些类型的癌症中可能具有潜在的诊断和预后作用；特别是结直肠癌，前提是这些结果在更大规模的多中心研究中得到实验验证和确认。
