CSF3R-AS promotes hepatocellular carcinoma progression and sorafenib resistance through the CSF3R/JAK2/STAT3 positive

Ziyang Feng1,2,3, Yan Gao1, Changjing Cai1

  • 1Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

Cell Death & Disease
|March 29, 2025
PubMed

Insights

Antisense circular RNA CSF3R-AS promotes hepatocellular carcinoma (HCC) growth and metastasis by stabilizing CSF3R mRNA and activating the JAK2/STAT3 pathway. This feedback loop also drives sorafenib resistance in HCC.

Area of Science:

  • Molecular Biology
  • Oncology
  • RNA Biology

Background:

  • Antisense circular RNAs (circRNAs) are emerging regulators of gene expression.
  • The role of antisense circRNAs in hepatocellular carcinoma (HCC) remains largely unexplored.

Purpose of the Study:

  • To investigate the function of antisense circRNA CSF3R-AS in HCC.
  • To elucidate the underlying molecular mechanisms and therapeutic potential in HCC.

Main Methods:

  • Quantitative real-time PCR to assess CSF3R-AS expression.
  • Cell proliferation, angiogenesis, and metastasis assays.
  • Western blotting and luciferase reporter assays to investigate signaling pathways.

Main Results:

  • CSF3R-AS was significantly upregulated in HCC tissues and correlated with poor prognosis.
  • CSF3R-AS promoted HCC cell proliferation, angiogenesis, and metastasis while inhibiting apoptosis.
  • CSF3R-AS directly binds to CSF3R mRNA, stabilizing it and activating the JAK2/STAT3 pathway, forming a positive feedback loop.

Conclusions:

  • The CSF3R-AS/CSF3R/JAK2/STAT3 positive feedback loop drives HCC progression and sorafenib resistance.
  • Targeting this loop presents a potential therapeutic strategy for HCC treatment and overcoming drug resistance.

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