Jin Hui-Fang, Wang Ju-Feng, Shao Ming, Zhou Kailu, Ma Xiao, Lv Xian-Ping
Department of Bloood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
Front Cell Dev Biol. 2020 Sep 22;8:555937. doi: 10.3389/fcell.2020.555937. eCollection 2020.
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.
微小RNA（miRNA）在多种癌症类型中表达失调，这使其在异常表达的患者中成为潜在的理想诊断或治疗靶点。在本研究中，我们发现miR-7在胃癌（GC）中表达下调，并且我们进一步确定其表达与GC对化疗化合物顺铂的敏感性密切相关。这种效应似乎至少部分归因于对乳酸脱氢酶A（LDH-A）的调控，LDH-A是miR-7的靶基因，并且在原发性GC肿瘤样本中LDH-A的表达与miR-7的表达呈负相关。当miR-7上调时，我们还确定它能够通过对LDH-A的调控来抑制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。因此，我们的结果提供了新的证据，表明miR-7通过对LDH-A的调控是GC生长和化疗敏感性的关键调节因子，从而可能突出该途径作为治疗受影响患者的治疗靶点。
