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MicroRNA-544 inhibits esophageal squamous cell carcinoma cell proliferation and enhances sensitivity to cisplatin by repressing E2F transcription factor 5

机译:MicroRNA-544通过抑制E2F转录因子5抑制食管鳞状细胞癌细胞增殖并增强对顺铂的敏感性

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摘要

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. MicroRNA (miRNA)-544 is an important cancer-associated RNA that is downregulated in multiple types of cancer. However, the role of miR-544 in ESCC progression remains unknown. In the present study, miR-544 expression level was determined via RT-qPCR in 30 pairs of ESCC and adjacent normal tissues and in a panel of ESCC cell lines. Cell proliferation and cell apoptosis were assessed by MTT and flow cytometry assays. Luciferase reporter assay and western blot analysis were conducted to verify E2F transcription factor 5 (E2F5), an oncogene in ESCC, as a novel target gene of miR-544. The results illustrated that miR-544 is frequently downregulated in ESCC tissues and cell lines. Overexpression of miR-544 in ESCC cells resulted in decreased cell proliferation and increased cell apoptosis. Thus, E2F5 was identified as a target of miR-544, and its expression was negatively correlated with miR-544 expression in clinical ESCC tissues. More importantly, overexpression of miR-544 led to increased sensitivity of ESCC cells to cisplatin, an anticancer drug. Overall, these findings indicate that miR-544 serves as a tumor suppressor by targeting E2F5; thus, miR-544 may be a therapeutic target for the treatment of ESCC.
机译:食道鳞状细胞癌(ESCC)是全球最常见的恶性肿瘤之一。 MicroRNA(miRNA)-544是一种重要的与癌症相关的RNA,在多种类型的癌症中均被下调。但是,miR-544在ESCC进展中的作用仍然未知。在本研究中,通过RT-qPCR测定了30对ESCC和邻近正常组织以及一组ESCC细胞系中的miR-544表达水平。通过MTT和流式细胞术分析评估细胞增殖和细胞凋亡。进行荧光素酶报告基因测定和蛋白质印迹分析以验证E2F转录因子5(E2F5),它是ESCC中的癌基因,是miR-544的新靶标基因。结果表明,miR-544在ESCC组织和细胞系中经常下调。 miR-544在ESCC细胞中的过表达导致细胞增殖减少和细胞凋亡增加。因此,E2F5被确定为miR-544的靶标,并且其表达与临床ESCC组织中的miR-544表达负相关。更重要的是,miR-544的过度表达导致ESCC细胞对顺铂(一种抗癌药物)的敏感性增加。总体而言,这些发现表明miR-544通过靶向E2F5来充当肿瘤抑制因子。因此,miR-544可能是ESCC的治疗靶标。

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