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Abstract <p>Liver cancer represents the third leading cause of cancer-related mortality globally, with hepatocellular carcinoma (HCC) accounting for the majority of cases. Despite a range of treatment options, the prognosis for advanced HCC remains poor, underscoring the need for further investigation into its pathogenic mechanisms and identification of potential therapeutic targets. Interferon γ (IFNγ) plays a crucial and multifaceted role in the occurrence and development of tumors. During tumorigenesis, alterations in miRNA expression occur, leading to subsequent changes in the expression of downstream target genes. However, the precise mechanism through which IFNγ exerts its effect via miRNA remains incompletely understood. In this study, high-throughput sequencing was employed to explore the miRNAs regulated by IFNγ in an HCC cell line. The results revealed that IFNγ regulates 17 uncharacterized miRNAs and 30 named miRNAs identified in the miRNA database. Among the miRNAs regulated by IFNγ, miR-1291 emerged as a prominent candidate. This study observed that miR-1291, along with KANSL2 mRNA and protein, is significantly upregulated in HepG2 and Huh7 cells. To investigate the role of miR-1291, HepG2 cells with both overexpression and inhibition of miR-1291 were established. High-throughput sequencing was then performed to examine the functional impact of miR-1291. The sequencing results revealed that genes regulated by miR-1291 are involved in cell cycle regulation and DNA replication. These findings were validated through qRT-PCR, cell proliferation assays, and colony formation assays, all of which confirmed that miR-1291 promotes HepG2 cell proliferation. Further analysis using a luciferase reporter assay and Western blot confirmed that SOCS3 is a direct target of miR-1291. Additionally, Western blot experiments demonstrated that miR-1291 promotes phosphorylation of the JAK/STAT signaling pathway by targeting SOCS3. These observations provide compelling evidence that IFNγ exerts its effects through the coordinated regulation of gene transcription and miRNA expression, shedding new light on the immune regulation of HCC. Furthermore, miR-1291 holds promise as a novel therapeutic target for liver cancer treatment.</p>

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IFNγ Upregulating miR-1291 Promotes Cell Proliferation and Enhances Phosphorylation of the JAK/STAT Signaling Pathway by Targeting SOCS3 in HepG2 Cells

  • 期刊论文

  • 发表日期：

    2025年7月21日

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  • X. Q. Li,
  • F. F. Peng,
  • Y. T. Xu,
  • L. R. Chen,
  • K. Lan,
  • F. N. Hu,
  • Y. Long,
  • S. H. Wang,
  • D. X. Lu,
  • X. Y. Huang,
  • Z. J. Huang,
  • L. L. Chen,
  • X. Q. Qin,
  • M. C. Qin

摘要

Abstract

Liver cancer represents the third leading cause of cancer-related mortality globally, with hepatocellular carcinoma (HCC) accounting for the majority of cases. Despite a range of treatment options, the prognosis for advanced HCC remains poor, underscoring the need for further investigation into its pathogenic mechanisms and identification of potential therapeutic targets. Interferon γ (IFNγ) plays a crucial and multifaceted role in the occurrence and development of tumors. During tumorigenesis, alterations in miRNA expression occur, leading to subsequent changes in the expression of downstream target genes. However, the precise mechanism through which IFNγ exerts its effect via miRNA remains incompletely understood. In this study, high-throughput sequencing was employed to explore the miRNAs regulated by IFNγ in an HCC cell line. The results revealed that IFNγ regulates 17 uncharacterized miRNAs and 30 named miRNAs identified in the miRNA database. Among the miRNAs regulated by IFNγ, miR-1291 emerged as a prominent candidate. This study observed that miR-1291, along with KANSL2 mRNA and protein, is significantly upregulated in HepG2 and Huh7 cells. To investigate the role of miR-1291, HepG2 cells with both overexpression and inhibition of miR-1291 were established. High-throughput sequencing was then performed to examine the functional impact of miR-1291. The sequencing results revealed that genes regulated by miR-1291 are involved in cell cycle regulation and DNA replication. These findings were validated through qRT-PCR, cell proliferation assays, and colony formation assays, all of which confirmed that miR-1291 promotes HepG2 cell proliferation. Further analysis using a luciferase reporter assay and Western blot confirmed that SOCS3 is a direct target of miR-1291. Additionally, Western blot experiments demonstrated that miR-1291 promotes phosphorylation of the JAK/STAT signaling pathway by targeting SOCS3. These observations provide compelling evidence that IFNγ exerts its effects through the coordinated regulation of gene transcription and miRNA expression, shedding new light on the immune regulation of HCC. Furthermore, miR-1291 holds promise as a novel therapeutic target for liver cancer treatment.