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Identification and validation of potential key long noncoding RNAs in sorafenib-resistant hepatocellular carcinoma

Manya Wu1,2, Xiaoyun Shen3, Yanping Tang1

  • 1Research Department, Guangxi Medical University Cancer Hospital, Nanning, China.

Peerj
|March 10, 2020
PubMed

Insights

This study reveals altered long noncoding RNA (lncRNA) expression in sorafenib-resistant liver cancer (HCC). Specific lncRNAs, TCONS_00284048 and TCONS_00006019, promote resistance, suggesting new therapeutic targets for HCC.

Area of Science:

  • * Oncology
  • * Molecular Biology
  • * Genomics

Background:

  • * Sorafenib is a first-line treatment for advanced hepatocellular carcinoma (HCC).
  • * Chemoresistance to sorafenib limits its clinical efficacy in HCC treatment.
  • * Understanding resistance mechanisms is crucial for improving HCC therapy.

Purpose of the Study:

  • * To investigate genome-wide long noncoding RNA (lncRNA) expression patterns in sorafenib-resistant HCC.
  • * To identify specific lncRNAs involved in sorafenib resistance in HCC.
  • * To explore the functional role of differentially expressed lncRNAs in HCC progression and resistance.

Main Methods:

  • * High-throughput sequencing to identify differentially expressed lncRNAs in sorafenib-resistant HCC cell lines (Huh7-S, HepG2-S) compared to parental cells.
  • * Gene Ontology (GO) term enrichment analysis to understand the functions of differentially expressed lncRNAs.
  • * Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify related signaling pathways.
  • * LncRNA knockdown experiments to assess their impact on sorafenib sensitivity.

Main Results:

  • * Thousands of differentially expressed lncRNAs were identified in sorafenib-resistant HCC cells.
  • * Enriched GO terms indicated involvement in binding, catalytic activity, and metabolic processes.
  • * KEGG pathway analysis highlighted the tight junction pathway.
  • * Upregulated lncRNAs TCONS_00284048 and TCONS_00006019 were consistently found in resistant cells.
  • * Knockdown of these lncRNAs increased sorafenib sensitivity in HCC cells.

Conclusions:

  • * LncRNA expression profiles are significantly altered in sorafenib-resistant HCC.
  • * Specific differentially expressed lncRNAs play critical roles in HCC sorafenib resistance.
  • * These lncRNAs may serve as potential therapeutic targets for overcoming sorafenib resistance and improving HCC progression outcomes.
Keywords:
Global transcriptomicHepatocellular carcinomaLong noncoding RNASorafenib-resistance

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