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Updated: Sep 15, 2025

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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A LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in

Lei Xu1, Haoyong Kuang2, Haodong Peng2

  • 1Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, 450003, China.

Cancer Cell International
|July 16, 2025
PubMed
Abstract

Insights

Researchers discovered a small protein from the LINC00472 long non-coding RNA (lncRNA) that fights non-small cell lung cancer (NSCLC). This LINC00472-encoded polypeptide (LINC00472-ORF) shows therapeutic potential by targeting the HDAC2/SP1 pathway.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • Long non-coding RNAs (lncRNAs) are emerging as sources of functional micropeptides.
  • The role of lncRNA-encoded polypeptides in non-small cell lung cancer (NSCLC) is not well understood.

Purpose of the Study:

  • To investigate the therapeutic potential of a polypeptide encoded by LINC00472 in NSCLC.
  • To elucidate the molecular mechanism underlying the anti-cancer effects of LINC00472-encoded polypeptide.

Main Methods:

  • Integrated multi-omics (ribosome profiling, transcriptomics) to identify lncRNA-encoded polypeptides.
  • Validated translational competence using ribosome affinity purification (TRAP), Western blot, and immunofluorescence.
  • Assessed anti-tumor effects through in vitro functional assays and in vivo xenograft models.
  • Analyzed protein interactions (HDAC2/SP1) using co-immunoprecipitation and luciferase reporter assays.

Main Results:

  • Identified LINC00472 as a bifunctional transcript encoding a 15-amino acid polypeptide (LINC00472-ORF).
  • LINC00472-ORF demonstrated significant tumor-suppressive activity, inhibiting NSCLC proliferation and motility in vitro and xenograft growth in vivo.
  • Discovered that LINC00472-ORF disrupts the HDAC2/SP1 interaction, leading to SP1 hyperacetylation and inactivation of oncogenic gene transcription.

Conclusions:

  • LINC00472-ORF acts as a dual-function therapeutic agent against NSCLC.
  • The mechanism involves targeting the HDAC2/SP1 axis to suppress tumor progression.
Keywords:
Epigenetic-transcriptional regulationHDAC2/SP1 axisLINC00472Multi-omics screeningNSCLClncRNA-encoded polypeptide

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