H1.0 modulates IL-6 expression and paclitaxel resistance via HDAC5 in ovarian cancer cells

Shang-Lang Huang ¹, Ting-Chang Chang ², Nian-Kang Sun ³

⁰Division of Biomedical Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China; Center for Drug Research and Development, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China.

Biochemical Pharmacology +

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March 20, 2025

View abstract on PubMed

Summary

Linker histone H1.0 promotes paclitaxel resistance in ovarian cancer by regulating IL-6 via HDAC5. This interplay highlights H1.0, HDAC5, and IL-6 as potential therapeutic targets to overcome chemoresistance.

Area Of Science

Molecular Biology
Cancer Research
Epigenetics

Background

Chemoresistance, particularly paclitaxel resistance (TXR), is a major obstacle in ovarian cancer treatment, leading to recurrence and metastasis.
Linker histone H1.0's role in cancer progression and drug resistance is increasingly recognized.
Histone deacetylase 5 (HDAC5) is implicated in gene regulation and cancer, but its specific role in chemoresistance is not fully understood.

Purpose Of The Study

To elucidate the role of linker histone H1.0 in paclitaxel resistance (TXR) in ovarian cancer cells.
To investigate the molecular mechanisms by which H1.0 influences chemoresistance, focusing on its interaction with HDAC5 and IL-6.
To identify potential therapeutic targets for overcoming paclitaxel resistance in ovarian cancer.

Main Methods

Transcriptomic profiling to identify pathways correlated with H1.0 expression.
Gain- and loss-of-function experiments for H1.0 expression.
Analysis of HDAC5 expression and its functional impact on cell viability and IL-6 levels.
Chromatin immunoprecipitation (ChIP) assays to assess histone acetylation and transcription factor binding.

Main Results

H1.0 expression is linked to enriched cytokine signaling pathways, particularly interleukin 6 (IL-6).
H1.0 regulates IL-6 mRNA and protein expression in ovarian cancer cells.
HDAC5 expression is inversely correlated with H1.0 and IL-6 levels; HDAC5 overexpression inhibits cell survival and reduces IL-6.
HDAC5 overexpression decreases H3K9Ac acetylation and NF-κB binding on the IL-6 promoter.

Conclusions

An interplay exists between H1.0, HDAC5, and IL-6 in mediating paclitaxel resistance in ovarian cancer.
H1.0 promotes chemoresistance by downregulating HDAC5, leading to increased IL-6 expression.
Targeting the H1.0-HDAC5-IL-6 axis presents a promising therapeutic strategy to overcome chemoresistance in ovarian cancer.

Keywords:

H1.0 HDAC5 IL-6 NF-κB Ovarian cancer Paclitaxel

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