lncRNA-POIR promotes epithelial-mesenchymal transition and suppresses sorafenib sensitivity simultaneously in hepatocellular carcinoma by sponging miR-182-5p.,Journal of Cellular Biochemistry

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lncRNA-POIR promotes epithelial-mesenchymal transition and suppresses sorafenib sensitivity simultaneously in hepatocellular carcinoma by sponging miR-182-5p.
Journal of Cellular Biochemistry ( IF 3.0 ) Pub Date : 2020-09-20 , DOI: 10.1002/jcb.29844
Bryan Wei Chen _{1,

2} , Yue Zhou _{1,

2} , Tao Wei _{1,

2} , Liang Wen _{1,

2} , Yi-Bo Zhang _{1,

2} , Shi-Chao Shen _{1,

2} , Jian Zhang _{1,

2} , Tao Ma _{1,

2} , Wen Chen _{1,

2} , Lei Ni _{1,

2} , Yi Wang _{1,

2} , Xue-Li Bai _{1,

2} , Ting-Bo Liang _{1,

2}

Affiliation

Sorafenib (SOR) resistance remains a major obstacle in the effective treatment of hepatocellular carcinoma (HCC). A number of long noncoding RNAs (lncRNAs) are responsible for this chemoresistance. This study aimed to reveal the essential function of a recently defined lncRNA, lncRNA‐POIR, in the epithelial–mesenchymal transition (EMT) and SOR sensitivity of HCC cells. SOR‐induced cytotoxicity was analyzed via cell counting kit‐8 and ethynyl‐2'‐deoxyuridine incorporation assays, whereas immunoblotting and confocal immunofluorescence were used to determine the expression levels of EMT markers. Furthermore, loss‐ or gain‐of‐function approaches were used to demonstrate the role of lncRNA‐POIR/miR‐182‐5p on EMT and SOR sensitivity in HCC. The direct interaction between lncRNA‐POIR and miR‐182‐5p was verified using a luciferase reporter assay. We found that knockdown of lncRNA‐POIR sensitized HCC cells to SOR and simultaneously reversed EMT. As expected, miR‐182‐5p was confirmed as the downstream target of lncRNA‐POIR. Moreover, miR‐182‐5p overexpression clearly reversed EMT and promoted SOR‐induced cytotoxicity in representative HCC cells, whereas miR‐182‐5p downregulation played a contrasting role; miR‐182‐5p knockdown abolished the modulatory effects of lncRNA‐POIR siRNA on EMT and SOR sensitivity. Together, these pieces of data suggest that lncRNA‐POIR promotes EMT progression and suppresses SOR sensitivity simultaneously by sponging miR‐182‐5p. Thus, we proposed a compelling rationale for the use of lncRNA‐POIR as a promising predictor of SOR response and as a potential therapeutic target for HCC treatment in the future.

中文翻译：

lncRNA-POIR通过刺激miR-182-5p在肝细胞癌中同时促进上皮-间质转化并抑制索拉非尼敏感性。

索拉非尼（SOR）耐药性仍然是有效治疗肝细胞癌（HCC）的主要障碍。许多长的非编码RNA（lncRNA）导致这种化学抗性。这项研究旨在揭示最近定义的lncRNA，lncRNA-POIR在肝癌上皮-间充质转化（EMT）和SOR敏感性中的基本功能。通过细胞计数试剂盒8和乙炔基2'-脱氧尿苷掺入分析法分析了SOR诱导的细胞毒性，而免疫印迹和共聚焦免疫荧光法则用于确定EMT标记物的表达水平。此外，使用功能丧失或获得功能的方法来证明lncRNA-POIR / miR-182-5p对肝癌EMT和SOR敏感性的作用。lncRNA-POIR和miR-182-5p之间的直接相互作用已通过萤光素酶报告基因检测得以验证。我们发现敲低lncRNA-POIR使HCC细胞对SOR敏感并同时逆转了EMT。与预期的一样，miR‐182‐5p被确认为lncRNA‐POIR的下游靶标。此外，miR-1182-5p的过度表达明显逆转了EMT并促进了代表HCC细胞中SOR诱导的细胞毒性，而miR-1182-5p的下调起到了相反的作用。miR‐182‐5p敲低取消了lncRNA‐POIR siRNA对EMT和SOR敏感性的调节作用。这些数据共同表明，lncRNA‐POIR通过使miR‐182‐5p海绵化，可促进EMT进展并同时抑制SOR敏感性。因此，我们提出了使用lncRNA-POIR作为SOR反应的有希望的预测指标以及将来作为HCC治疗的潜在治疗靶标的令人信服的理由。

更新日期：2020-09-20

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