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Knockdown of miR-106a suppresses migration and invasion and enhances radiosensitivity of hepatocellular carcinoma cells by upregulating FBXW7

机译:抑制miR-106a通过上调FBXW7抑制迁移和侵袭并增强肝癌细胞的放射敏感性

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摘要

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. microRNAs (miRNAs) have been reported to play essential roles in HCC progression and radiosensitivity. However, the effect of miR-106a on HCC progression and radiosensitivity as well as its mechanism remain largely unknown. The expressions of miR-106a and F-box and WD repeat domain containing 7 (FBXW7) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot, respectively. Cell migration and invasion were analyzed by trans-well assay. The radiosensitivity was investigated by colony formation and western blot. The interaction between miR-106a and FBXW7 was explored by luciferase activity and RNA immunoprecipitation (RIP) analyses. Then miR-106a expression was elevated in HCC tissues and cells and associated with tumor stage as well as overall survival. Knockdown of miR-106a impeded cell migration and invasion but contributed to irradiation-induced inhibition of survival and increase of phosphorylation of histone in Serine 139 (γ-H2AX) protein in HCC cells. Moreover, FBXW7 was indicated as a target of miR-106a and negatively correlated with miR-106a. Besides, interference of FBXW7 reversed the regulatory effect of miR-106a abrogation on migration, invasion and radiosensitivity in HCC cells. The results showed down-regulation of miR-106a suppressed migration and invasion and increased radiosensitivity of HCC cells by targeting FBXW7, providing a novel avenue for HCC treatment.
机译:肝细胞癌(HCC)是全球最常见的癌症之一。据报道,microRNA(miRNA)在HCC进展和放射敏感性中起着至关重要的作用。然而,miR-106a对HCC进展和放射敏感性的影响及其机制仍然未知。分别通过定量实时聚合酶链反应(qRT-PCR)或western blot检测miR-106a和含7个F-box和WD重复结构域的表达。细胞迁移和侵袭通过trans-well测定法进行分析。通过菌落形成和蛋白质印迹研究放射敏感性。通过荧光素酶活性和RNA免疫沉淀(RIP)分析探索了miR-106a与FBXW7之间的相互作用。然后,miR-106a在肝癌组织和细胞中的表达升高,并且与肿瘤分期以及总生存期有关。敲低miR-106a阻止细胞迁移和侵袭,但有助于辐射诱导的HCC细胞中丝氨酸139(γ-H2AX)蛋白的存活抑制和组蛋白磷酸化的增加。此外,FBXW7被指示为miR-106a的靶标,并且与miR-106a负相关。此外,FBXW7的干扰逆转了miR-106a取消对HCC细胞迁移,侵袭和放射敏感性的调节作用。结果表明,miR-106a的下调通过靶向FBXW7抑制了HCC细胞的迁移和侵袭,并增加了放射敏感性,为HCC治疗提供了新途径。

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