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Components of the JNK-MAPK pathway play distinct roles in hepatocellular carcinoma

Jijun Yu1,2, Xinying Li2, Junxia Cao3

  • 1School of Basic Medicine, Hainan Medical University, Haikou, 571199, China.

Journal of Cancer Research and Clinical Oncology
|October 30, 2023
PubMed
Abstract

Insights

Targeting MKK7 may be a promising strategy for hepatocellular carcinoma (HCC) therapy. This study found MKK7 upregulation in HCC and demonstrated that MKK7 knockdown inhibits HCC cell growth and enhances apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Signal Transduction

Background:

  • Mitogen-activated protein kinases (MAPK), particularly the c-Jun N-terminal kinase (JNK)-MAPK subfamily, are implicated in various cancers, including hepatocellular carcinoma (HCC).
  • The precise roles of JNK1/2 and their upstream regulators, MKK4 and MKK7, in HCC development are not fully understood.

Purpose of the Study:

  • To investigate the expression patterns and functional significance of JNK-MAPK pathway components in HCC.
  • To evaluate the prognostic value of JNK-MAPK components in HCC.
  • To explore the therapeutic potential of targeting the JNK-MAPK pathway in HCC.

Main Methods:

  • Differential gene and protein expression analysis using TCGA and HPA databases.
  • Prognostic evaluation using Kaplan-Meier survival and ROC curve analyses.
  • Functional assays including immunoblotting, apoptosis analysis (FACS), and soft agar assays in HCC cell lines under various death stimuli.

Main Results:

  • JNK1/2 and MKK7 were upregulated, while MKK4 was downregulated in HCC tissues.
  • JNK2 and MKK7 showed potential as diagnostic markers for HCC, with high JNK2 expression correlating with poor survival.
  • MKK7 knockdown significantly enhanced apoptosis and inhibited colony formation in HCC cells, suggesting a critical role in HCC progression.

Conclusions:

  • MKK7 is a key driver in HCC progression and a potential therapeutic target.
  • Targeting MKK7 offers a promising strategy for HCC treatment, potentially more effective than targeting JNK1/2 or MKK4.
Keywords:
ApoptosisHepatocellular carcinomaJNK–MAPK signaling pathwayMKK7

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