miR125a在HER-2阳性胃癌中的分子特征及潜在治疗作用分析
Molecular characterization and potential therapeutic roles of miR125a in HER-2 positive gastric cancer.
发表日期:2023
作者:
Afraa Mamoori, Zena Hasan Sahib, Haider Alkafaji
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
本研究旨在研究miR-125a-3p在胃癌中的表达模式,确定其靶基因在胃癌组织中的表达水平,并测试其对HER-2阳性胃癌细胞的作用。使用Real-time PCR在70例胃癌组织中测量miR-125a-3p的水平。通过免疫组织化学研究测量这些胃癌组织中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。通过体外研究分析了miR-125a-3p单独和与5-FU(氟尿嘧啶)联合对HER2阳性(NUGC4)和HER2阴性(ECC10)胃癌细胞生长的影响。大多数胃癌组织样本与其非癌组织相比,miR-125a-3p表达下调(84%)。miR-125a-3p表达下调与胃癌复发和病理分期显著相关(P = 0.02和0.02,分别)。HER2蛋白表达与miR-125a-3p表达显著负相关(P < 0.05)。与其他对照组细胞相比,转染miR-125a-3p的胃癌细胞在添加5-FU后细胞生长速率显著降低(P < 0.01)。当两种胃癌细胞株转染miR-125a-3p后,HER2阳性(NUGC4)细胞系的细胞生长抑制率显著高于HER2阴性(ECC10)细胞(P < 0.01)。miR-125a-3p在胃癌的发病机制中起着重要的作用。对HER2阳性胃癌细胞进行miR-125a-3p的治疗转染导致细胞增殖减少,并增强5-FU的作用。
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.