Abstract
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. Our research aimed to explore the function and molecular mechanism of lncRNA PCGEM1 on oxaliplatin resistance of HCC in vitro. 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. 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. 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.
Highlights
Hepatocellular carcinoma (HCC) is one of the most severe malignant cancers that leads to high death rate worldwide
Our data indicated that PCGEM1 and ETV1 expression were enhanced in Hep3B/OXA cells
Our findings demonstrated that PCGEM1 modulated oxaliplatin resistance by targeting the miR129-5p/ETV1 pathway in HCC in vitro, suggesting a potential strategy for the treatment of chemoresistant HCC
Summary
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. Hepatocellular carcinoma (HCC) is a severe type of malignant tumor, leading to a large number of cancer-related deaths worldwide.[1,2] It is an invasive and fast-growing tumor that leads to higher recurrence and metastasis.[3] Despite advancements in the therapeutic techniques for HCC such as radiotherapy, chemotherapy and surgery, the prognosis is still unsatisfactory, with an overall five-year survival rate of 15−40%.4,5. Along with the progression of microarray analysis and sequencing, numerous novel non-coding RNAs have been discovered. Whether lncRNA PCGEM1 exerts its function in the development and tumorigenesis of HCC remains unknown
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