Mamoori Afraa, Sahib Zena Hasan, Alkafaji Haider
Department of Pathology and Forensic Medicine, School of Medicine, University of Babylon, Iraq.
Department of Pharmacology, Hammurabi College of Medicine, University of Babylon, Iraq.
Indian J Pathol Microbiol. 2023 Jul-Sep;66(3):472-477. doi: 10.4103/ijpm.ijpm_580_21.
miR-125a-3p could have a role in gastric cancer by targeting HER2. This study aimed to investigate the expression pattern of miR-125a-3p, identify the expression level of its target gene in gastric carcinoma, and test its effect in HER-2 positive gastric carcinoma cells.
The levels of miR-125a-3p in both cancer and noncancer tissues were measured by using Quantitative real-time polymerase chain in 70 gastric carcinomas. Immunohistochemical study was used to measure the expression of HER2 protein in these carcinomas. In addition, the level of expression of this miRNA is correlated to different pathological and clinical parameters. The effects of miR-125a-3p alone and in combination with 5-FU (fluorouracil) on the growth of HER2 positive (NUGC4) and HER2 negative (ECC10) gastric carcinoma cells were also analyzed by in vitro studies.
Most gastric cancer tissues samples showed downregulation of miR-125a-3p (84%) when compared to their noncancer tissues. Significant correlations of downregulation of miR-125a-3p with cancer recurrence and pathological staging of gastric carcinoma (P = 0. 02 and 0.02, respectively) were noted. HER2 protein expression correlated significantly and inversely with miR-125a-3p expression (P < 0.05). A reduction in cell growth rate was noted significantly in miR-125a-3p transfected gastric carcinoma cells when 5-FU was added to them in comparison to other control cells (P < 0.01). When both gastric carcinoma cell lines were transfected with miR-125a-3p, a significantly higher growth inhibition percentage in HER2 positive (NUGC4) cell line was seen in comparison to the HER2 negative (ECC10) cells (P < 0.01).
miR-125a-3p plays a significant role in the pathogenesis of gastric carcinoma. Therapeutic transfection of miR-125a-3p in HER2 positive gastric cancer cells resulted in reduced cell proliferation and potentiate the effect of 5-FU.
miR-125a-3p可能通过靶向HER2在胃癌中发挥作用。本研究旨在调查miR-125a-3p的表达模式，确定其靶基因在胃癌中的表达水平，并测试其在HER-2阳性胃癌细胞中的作用。
使用定量实时聚合酶链反应检测70例胃癌组织及癌旁组织中miR-125a-3p的水平。采用免疫组织化学研究检测这些癌组织中HER2蛋白的表达。此外，该miRNA的表达水平与不同的病理和临床参数相关。还通过体外研究分析了单独的miR-125a-3p以及与5-氟尿嘧啶（5-FU）联合使用对HER2阳性（NUGC4）和HER2阴性（ECC10）胃癌细胞生长的影响。
与癌旁组织相比，大多数胃癌组织样本显示miR-125a-3p下调（84%）。注意到miR-125a-3p下调与胃癌复发和病理分期显著相关（分别为P = 0.02和0.02）。HER2蛋白表达与miR-125a-3p表达显著负相关（P < 0.05）。与其他对照细胞相比，当向转染了miR-125a-3p的胃癌细胞中加入5-FU时，细胞生长速率显著降低（P < 0.01）。当两种胃癌细胞系都转染miR-125a-3p时，与HER2阴性（ECC-10）细胞相比，HER2阳性（NUGC4）细胞系中观察到显著更高的生长抑制率（P < 0.01）。
miR-125a-3p在胃癌发病机制中起重要作用。在HER2阳性胃癌细胞中进行miR-125a-3p的治疗性转染可导致细胞增殖减少，并增强5-FU的作用。
