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DHX33 inhibitors induced transcriptional changes for a subset of genes in cancer cells

Xingshun Wang1, Yichu Fu2, Xiyu Tang3

  • 1School of Health and Nursing, Yunnan Open University, Kunming, 650500, Yunnan, China.

Scientific Reports
|June 4, 2026
PubMed

Insights

Small molecule inhibitors targeting RNA helicase DHX33 (RHA) activity mimic gene expression changes seen with DHX33 knockdown. This suggests DHX33

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Drug Discovery

Background:

  • RNA helicase DHX33 (RHA) is implicated in cancer development.
  • The role of DHX33's helicase activity in its cellular functions is not fully understood.

Purpose of the Study:

  • To investigate whether DHX33's helicase activity is essential for its role in regulating gene transcription in cancer cells.
  • To compare the effects of DHX33 helicase inhibition with DHX33 knockdown on gene expression.

Main Methods:

  • Utilized small molecule inhibitors (BCD38 and KY386) targeting DHX33 helicase activity.
  • Performed gene transcriptional profiling upon inhibitor treatment and compared with DHX33 knockdown data.
  • Evaluated effects in human cancer cells in vitro and in vivo.

Main Results:

  • DHX33 inhibitors induced transcriptional changes in a subset of genes, recapitulating DHX33 knockdown effects.
  • Inhibitors selectively downregulated genes associated with cancer progression.
  • Observed some discrepancies between inhibitor effects and knockdown, suggesting nuanced regulation.

Conclusions:

  • Targeting DHX33 helicase activity with small molecules induces gene expression changes mimicking DHX33 knockdown.
  • The cellular functions of DHX33 are dependent on its helicase activity.
  • Small molecule inhibitors offer a viable strategy to study and potentially target DHX33 in cancer.
Keywords:
DHX33InhibitorLung cancerOncogeneRNA helicase

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