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长链非编码 RNA PCGEM1 通过体外 miR-129-5p/ETV1 轴介导肝癌对奥沙利铂的耐药性。

LncRNA PCGEM1 mediates oxaliplatin resistance in hepatocellular carcinoma via miR-129-5p/ETV1 axis in vitro.

机构信息

Department Of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Department Of General Surgery, The Second Affiliated Hospital of Nantong University, China.

出版信息

Adv Clin Exp Med. 2021 Aug;30(8):831-838. doi: 10.17219/acem/135533.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the most severe malignant cancers that leads to high death rate worldwide. Recent research revealed that long non-coding RNAs (lncRNAs) exert a critical role regarding chemoresistance in numerous cancers, including HCC.

OBJECTIVES

Our research aimed to explore the function and molecular mechanism of lncRNA PCGEM1 on oxaliplatin resistance of HCC in vitro.

MATERIAL AND METHODS

Expression of the lncRNA PCGEM1, together with miR-129-5p, and the mRNA level of ETV1 and drug resistance-related genes including LRPA, MDR1 and MDR3 were determined using quantitative real-time polymerase chain reaction (qRT-PCR) in an oxaliplatin-resistant HCC cell line (Hep3B/OXA). Cell Counting Kit-8 (CCK-8) was employed to assess the viability and cell survival rate, and transwell assays were performed to measure the number of migrated or invaded cells. In addition, the relation among lncRNA PCGEM1, miR-129-5p and ETV1 were determined using luciferase assay.

RESULTS

Our data indicated that PCGEM1 and ETV1 expression were enhanced in Hep3B/OXA cells. Furthermore, knockdown of lncRNA PCGEM1 significantly decreased the migration, invasion and mRNA expressions of LRPA, MDR1 and MDR3, and the cell viability in Hep3B/OXA cells. The starBase online tool and luciferase assays verified that miR-129-5p targeted PCGEM1 and ETV1, signifying that PCGEM1 could enhance ETV1 expression via suppressing miR-129-5p.

CONCLUSIONS

Our findings demonstrated that PCGEM1 modulated oxaliplatin resistance by targeting the miR-129-5p/ETV1 pathway in HCC in vitro, suggesting a potential strategy for the treatment of chemoresistant HCC.

摘要

背景

肝细胞癌(HCC)是全球导致高死亡率的最严重恶性癌症之一。最近的研究表明,长链非编码 RNA(lncRNA)在包括 HCC 在内的许多癌症的化疗耐药性中发挥着关键作用。

目的

本研究旨在探讨 lncRNA PCGEM1 在体外 HCC 对奥沙利铂耐药中的作用和分子机制。

材料与方法

采用定量实时聚合酶链反应(qRT-PCR)检测奥沙利铂耐药 HCC 细胞系(Hep3B/OXA)中 lncRNA PCGEM1、miR-129-5p 的表达,以及 ETV1 和耐药相关基因(LRPA、MDR1 和 MDR3)的 mRNA 水平。采用细胞计数试剂盒-8(CCK-8)检测细胞活力和细胞存活率,Transwell 检测迁移和侵袭细胞数。此外,通过荧光素酶测定法确定 lncRNA PCGEM1、miR-129-5p 和 ETV1 之间的关系。

结果

我们的数据表明,PCGEM1 和 ETV1 在 Hep3B/OXA 细胞中表达增强。此外,lncRNA PCGEM1 敲低显著降低了 Hep3B/OXA 细胞的迁移、侵袭和 LRPA、MDR1 和 MDR3 的 mRNA 表达以及细胞活力。StarBase 在线工具和荧光素酶测定验证了 miR-129-5p 靶向 PCGEM1 和 ETV1,表明 PCGEM1 可以通过抑制 miR-129-5p 来增强 ETV1 的表达。

结论

本研究结果表明,PCGEM1 通过靶向 HCC 中的 miR-129-5p/ETV1 通路调节奥沙利铂耐药,为治疗化疗耐药 HCC 提供了一种潜在策略。

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