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<p> <!--Query ID="Q1" Text="Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary." Resolved="yes"-->This study aimed to characterize candidate regulatory networks associated with LINC02365 knockdown using integrative transcriptomic profiling and Huh-7 cells as a model of hepatocellular carcinoma. LINC02365 expression was evaluated in TCGA-LIHC and GEO datasets and validated in Huh-7, SMMC7721, MHCC97-H, and LO2 cell lines by qRT-PCR. Huh-7 cells with stable LINC02365 knockdown were subjected to next-generation RNA sequencing. Differential gene expression analysis, Gene Ontology (GO) enrichment, KEGG and Reactome pathway analysis, protein-protein interaction (PPI) analysis, transcription factor annotation, microRNA-related analysis, fusion gene detection, alternative splicing analysis, and immune-related signature profiling were performed to define candidate regulatory networks associated with LINC02365 knockdown. LINC02365 was consistently upregulated in TCGA-LIHC and GEO datasets and in the examined HCC cell lines. Transcriptomic profiling following LINC02365 knockdown revealed widespread changes in gene expression. GO enrichment analysis showed significant associations with epithelial cell proliferation, cell adhesion-related processes, transcription factor regulation, inflammatory response-related terms, and extracellular matrix-associated functions. KEGG pathway analysis identified PI3K-Akt signaling as the most prominent candidate downstream pathway, whereas Reactome analysis highlighted extracellular matrix organization. In addition, LINC02365 knockdown was associated with broad changes in transcription factor-linked networks, microRNA-related networks, alternative splicing events, fusion gene profiles, and immune-related transcriptional signatures. This integrative transcriptomic analysis suggests that LINC02365 is associated with multilayered transcriptomic and regulatory changes in Huh-7 cells and provides a discovery-oriented framework for future functional and mechanistic investigation in hepatocellular carcinoma.</p>

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Integrative transcriptomic profiling identifies LINC02365-associated regulatory networks in hepatocellular carcinoma

  • 期刊论文

  • 发表日期：

    2026年6月1日

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  • Peter Kisembo,
  • Christian Cedric Bongolo,
  • Mengqi Wei,
  • Feng Lian Liu,
  • Chang Wu,
  • Shanshan Gao,
  • Fang Zheng,
  • Simon Peter Rugera,
  • Jian Cheng Tu

摘要

This study aimed to characterize candidate regulatory networks associated with LINC02365 knockdown using integrative transcriptomic profiling and Huh-7 cells as a model of hepatocellular carcinoma. LINC02365 expression was evaluated in TCGA-LIHC and GEO datasets and validated in Huh-7, SMMC7721, MHCC97-H, and LO2 cell lines by qRT-PCR. Huh-7 cells with stable LINC02365 knockdown were subjected to next-generation RNA sequencing. Differential gene expression analysis, Gene Ontology (GO) enrichment, KEGG and Reactome pathway analysis, protein-protein interaction (PPI) analysis, transcription factor annotation, microRNA-related analysis, fusion gene detection, alternative splicing analysis, and immune-related signature profiling were performed to define candidate regulatory networks associated with LINC02365 knockdown. LINC02365 was consistently upregulated in TCGA-LIHC and GEO datasets and in the examined HCC cell lines. Transcriptomic profiling following LINC02365 knockdown revealed widespread changes in gene expression. GO enrichment analysis showed significant associations with epithelial cell proliferation, cell adhesion-related processes, transcription factor regulation, inflammatory response-related terms, and extracellular matrix-associated functions. KEGG pathway analysis identified PI3K-Akt signaling as the most prominent candidate downstream pathway, whereas Reactome analysis highlighted extracellular matrix organization. In addition, LINC02365 knockdown was associated with broad changes in transcription factor-linked networks, microRNA-related networks, alternative splicing events, fusion gene profiles, and immune-related transcriptional signatures. This integrative transcriptomic analysis suggests that LINC02365 is associated with multilayered transcriptomic and regulatory changes in Huh-7 cells and provides a discovery-oriented framework for future functional and mechanistic investigation in hepatocellular carcinoma.