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首页> 外文期刊>Cell biology international. >MicroRNA‐214 suppresses cell proliferation and migration and cell metabolism by targeting PDK2 and PHF6 in hepatocellular carcinoma
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MicroRNA‐214 suppresses cell proliferation and migration and cell metabolism by targeting PDK2 and PHF6 in hepatocellular carcinoma

机译：microRNA-214通过靶向PDK2和PHF6在肝细胞癌中抑制细胞增殖和迁移和细胞代谢

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摘要

Abstract MiR‐214 has been reported to act as a tumor suppressor or oncogene involved in various malignancies. However, the biological functions and molecular mechanisms of miR‐214 in hepatocellular carcinoma (HCC) still remain?unclear. Previous studies suggest that pyruvate dehydrogenase kinase 2 (PDK2) and plant homeodomain finger protein 6 (PHF6) may be involved in some tumor cell proliferation and migration. Therefore, we studied the relationship between PDK2/PHF6 and miR‐214. The expression of miR‐214, PDK2, and PHF6 was determined by quantitative real‐time polymerase chain reaction in HCC tissues and cell lines. The Luciferase reporter assay was used to confirm the interaction between miR‐214 and PDK2/PHF6. Cell proliferation, apoptosis, and migration were evaluated by cell counting kit‐8 assay, flow cytometry, and transwell assay, respectively. The expressions levels of α‐smooth muscle actin (α‐SMA) and E‐cadherin were detected via immunofluorescence assay. Here, we found that the expression of miR‐214 decreased in HCC and was negatively correlated with PDK2 and PHF6. Moreover, PDK2 and PHF6 were the direct targets of miR‐214 in HCC cells. Functional analysis showed that knockdown of PDK2 or PHF6?as well as miR‐214 overexpression significantly suppressed cell proliferation and migration in HCC cells. Furthermore, we found that the suppression of cell proliferation and migration through PDK2 or PHF6 knockdown could be partially reversed by miR‐214 down‐regulation. Moreover, we demonstrated a decrease of mesenchymal cell marker α‐SMA and increase of the epithelial marker E‐cadherin after miR‐214 overexpression, PDK2 knockdown or PHF6 knockdown, respectively, which also suggested that cell proliferation and migration were suppressed. Additionally, lactate and pyruvic acid production experiments confirmed miR‐214 could suppress the HCC cell lactate and pyruvic acid levels by down‐regulating PDK2/PHF6. In conclusion, MiR‐214 may act as a tumor suppressor gene, presenting its suppressive role in cell proliferation and migration of HCC cells by targeting PDK2 and PHF6, and?might provide a potential therapy target for patients with HCC.
机译：摘要据报道，MiR-214是一种与多种恶性肿瘤有关的抑癌基因。然而，miR-214在肝细胞癌（HCC）中的生物学功能和分子机制仍然存在？不清楚的。以往的研究表明，丙酮酸脱氢酶激酶2（PDK2）和植物同源结构域指状蛋白6（PHF6）可能参与某些肿瘤细胞的增殖和迁移。因此，我们研究了PDK2/PHF6和miR-214之间的关系。通过实时定量聚合酶链反应测定肝癌组织和细胞系中miR-214、PDK2和PHF6的表达。荧光素酶报告分析用于确认miR-214和PDK2/PHF6之间的相互作用。细胞增殖、凋亡和迁移分别通过细胞计数试剂盒-8分析、流式细胞术和transwell分析进行评估。通过免疫荧光法检测α-平滑肌肌动蛋白（α-SMA）和E-钙粘蛋白的表达水平。在这里，我们发现在HCC中miR-214的表达降低，并且与PDK2和PHF6呈负相关。此外，PDK2和PHF6是肝癌细胞中miR-214的直接靶点。功能分析显示PDK2或PHF6的敲除？miR-214的过度表达显著抑制了肝癌细胞的增殖和迁移。此外，我们发现通过PDK2或PHF6基因敲除抑制细胞增殖和迁移可以通过miR-214下调部分逆转。此外，我们还证明，在miR-214过度表达、PDK2基因敲除或PHF6基因敲除后，间充质细胞标记物α-SMA减少，上皮标记物E-钙粘蛋白增加，这也表明细胞增殖和迁移受到抑制。此外，乳酸和丙酮酸产生实验证实，miR-214可以通过下调PDK2/PHF6来抑制HCC细胞的乳酸和丙酮酸水平。总之，MiR-214可能作为肿瘤抑制基因发挥作用，通过靶向PDK2和PHF6在细胞增殖和HCC细胞迁移中发挥抑制作用，以及？可能为肝癌患者提供一个潜在的治疗靶点。

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  • 来源
    《Cell biology international.》 |2020年第1期|共10页
  • 作者

    Yu Qiangfeng; Zhou Jianyin; Jian Yizeng; Xiu Zhe; Xiang Leyang; Yang Dinghua; Zeng Wenlong;

  • 作者单位

    Department of Hepatobiliary Surgerythe Second Hospital of LongyanFujian 364000 China;

    Department of Hepatobiliary and Pancreatic Surgery Zhongshan HospitalXiamen UniversityXiamen;

    Department of Hepatobiliary Surgerythe Second Hospital of LongyanFujian 364000 China;

    Department of Hepatobiliary Surgerythe Second Hospital of LongyanFujian 364000 China;

    Department of Hepatobiliary SurgeryCancer Center of Guangzhou Medical UniversityGuangzhou 510095;

    Department of Hepatobiliary SurgeryNanfang Hospital Affiliated to Southern Medical;

    Department of Hepatobiliary Surgerythe Second Hospital of LongyanFujian 364000 China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    cell proliferation; HCC; migration; miR‐214; PDK2; PHF6;

    机译：细胞增殖;HCC;迁移;miR-214;pdk2;phf6;

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