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Triptolide Treatment for Oral Squamous Cell Carcinoma by Regulating the LncRNA-MSTRG.24214.1/MiRNA-939-5p/LCN2 Axis

Siyan Chen1,2, Zhengmiao Li1,2, Menglin Hu1,2

  • 1The First Affiliated Hospital of Harbin Medical University, School of Stomatology, Harbin Medical University, Harbin, China.

Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
|March 17, 2025
PubMed
Abstract

Insights

Triptolide effectively treats oral squamous cell carcinoma (OSCC) by modulating the MSTRG.24214.1-miR-939-5p-LCN2 axis, suppressing tumor growth and progression. This study clarifies its molecular mechanism for future therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oral squamous cell carcinoma (OSCC) remains a significant health concern with limited treatment options.
  • The precise molecular mechanisms of triptolide, a potential anti-cancer agent, in OSCC are not fully understood.
  • Investigating lncRNA-mediated competing endogenous RNA (ceRNA) networks offers a novel approach to elucidate triptolide's action.

Purpose of the Study:

  • To elucidate the molecular mechanism of triptolide in oral squamous cell carcinoma (OSCC) treatment.
  • To investigate the role of long non-coding RNA (lncRNA)-mediated competing endogenous RNA (ceRNA) networks in triptolide's efficacy.
  • To establish the lncRNA-miRNA-mRNA regulatory network influenced by triptolide in OSCC.

Main Methods:

  • In vivo xenograft tumor models were used to assess triptolide's effect on OSCC.
  • Whole-transcriptome sequencing and bioinformatics analysis were employed to construct the regulatory network.
  • Quantitative real-time PCR (qRT-PCR), Western blot, dual-luciferase assays, CCK8, wound healing, and transwell assays were utilized for validation and functional analysis.

Main Results:

  • Triptolide significantly inhibited OSCC cell proliferation, migration, and invasion in vitro.
  • Triptolide treatment led to tumor volume reduction in vivo, with increased cleaved Caspase-3 and Bax, and decreased Bcl-2.
  • Transcriptome analysis revealed differential expression of numerous mRNAs, lncRNAs, and miRNAs, highlighting the MSTRG.24214.1-miR-939-5p-LCN2 axis.

Conclusions:

  • A lncRNA-miRNA-mRNA ceRNA network involved in triptolide's anti-OSCC activity was successfully established.
  • Triptolide demonstrates potent anti-cancer effects against OSCC both in vitro and in vivo.
  • Modulation of the MSTRG.24214.1-miR-939-5p-LCN2 axis is a key mechanism underlying triptolide's therapeutic potential in OSCC.
Keywords:
LCN2MSTRG.24214.1OSCCTPLmiR‐939‐5p

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