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Down-Regulation of miR-7 in Gastric Cancer Is Associated With Elevated LDH-A Expression and Chemoresistance to Cisplatin
Frontiers in Cell and Developmental Biology ( IF 5.5 ) Pub Date : 2020-08-14 , DOI: 10.3389/fcell.2020.555937
Hui-Fang Jin , Ju-Feng Wang , Ming Shao , Kailu Zhou , Xiao Ma , Xian-Ping Lv

MicroRNAs (miRNAs) are dysregulated in the context of many cancer types, making them potentially ideal diagnostic or therapeutic targets in patients in which they are aberrantly expressed. In the present study, we found miR-7 to be downregulated in gastric cancer (GC), and we further determined its expression to be closely linked to GC sensitivity to the chemotherapeutic compound cisplatin. This effect appears to be at least partially attributable to the regulation of LDH-A, which is a miR-7 target gene and expression of LDH-A is negatively correlated with miR-7 expression in primary GC tumor samples. When upregulated, we also determined that miR-7 was able to inhibit the proliferation, colony formation, and glycolysis of GC cells owing to its regulation of LDH-A. Moreover, overexpression of miR-7 render cells more sensitive to cisplatin. Our results thus provide novel evidence that miR-7 is a key mediator of GC growth and chemosensitivity through its regulation of LDH-A, thus potentially highlighting this pathway as a therapeutic target for treating affected patients.



中文翻译:

miR-7在胃癌中的下调与LDH-A表达升高和对顺铂的化学耐药性相关

在许多癌症类型的情况下,microRNA(miRNA)失调,使其成为异常表达其的患者的潜在理想诊断或治疗靶标。在本研究中,我们发现miR-7在胃癌(GC)中被下调,并且我们进一步确定了其表达与GC对化疗化合物顺铂的敏感性密切相关。这种作用似乎至少部分归因于LDH-A的调控,LDH-A是miR-7的靶基因,LDH-A的表达与原发性GC肿瘤样品中的miR-7的表达呈负相关。当上调时,我们还确定了miR-7由于其对LDH-A的调节而能够抑制GC细胞的增殖,集落形成和糖酵解。此外,miR-7的过表达使细胞对顺铂更敏感。

更新日期:2020-09-22
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