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

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Hepatocellular carcinoma (HCC) is a major global health concern with complex regulatory mechanisms.
• Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development and progression.
• LINC02365 has been implicated in cancer, but its specific regulatory networks in HCC require detailed characterization.

Purpose of the Study:

• To investigate the candidate regulatory networks associated with LINC02365 knockdown in hepatocellular carcinoma.
• To characterize the transcriptomic alterations and downstream pathways affected by LINC02365 modulation in HCC cells.
• To provide a framework for understanding LINC02365's functional role in HCC pathogenesis.

Main Methods:

• Integrative transcriptomic profiling of Huh-7 hepatocellular carcinoma cells with stable LINC02365 knockdown.
• Expression analysis of LINC02365 in public datasets (TCGA-LIHC, GEO) and HCC cell lines using qRT-PCR.
• Comprehensive bioinformatic analyses including differential gene expression, Gene Ontology (GO), KEGG, Reactome pathway analysis, PPI network construction, and immune signature profiling.

Main Results:

• LINC02365 was consistently upregulated in HCC datasets and cell lines.
• Knockdown of LINC02365 induced significant transcriptomic changes, impacting epithelial cell proliferation, cell adhesion, and extracellular matrix functions.
• Key affected pathways included PI3K-Akt signaling and extracellular matrix organization, with alterations in transcription factor networks, microRNA interactions, splicing, fusion genes, and immune signatures.

Conclusions:

• LINC02365 is associated with multilayered transcriptomic and regulatory alterations in hepatocellular carcinoma cells.
• The findings highlight LINC02365's potential role in HCC pathogenesis through diverse molecular pathways.
• This study provides a foundation for future functional and mechanistic investigations into LINC02365 in HCC.