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NF-κB-mediated lncRNA AC007271.3 promotes carcinogenesis of oral squamous cell carcinoma by regulating

Ze-Nan Zheng1, Guang-Zhao Huang1, Qing-Qing Wu1

  • 1Department of Oral & Maxillofacial Surgery, NanFang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Cell Death & Disease
|December 14, 2020
PubMed

Insights

Long non-coding RNA AC007271.3 promotes oral cancer by activating the NF-κB pathway. This lncRNA (long non-coding RNA) regulates epithelial-mesenchymal transition via the miR-125b-2-3p/Slug/E-cadherin axis, offering a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oral squamous cell carcinoma (OSCC) is a prevalent cancer with incompletely understood molecular drivers.
  • Previous research identified long non-coding RNA (lncRNA) AC007271.3 as a prognostic marker and promoter of OSCC progression in vitro and in vivo.
  • The precise mechanisms underlying AC007271.3 dysregulation in OSCC remained unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which AC007271.3 contributes to OSCC development.
  • To investigate the role of AC007271.3 as a competing endogenous RNA (ceRNA) in OSCC.
  • To identify upstream regulators and downstream targets of AC007271.3 in the context of OSCC.

Main Methods:

  • Investigated AC007271.3's interaction with miR-125b-2-3p and its effect on Slug expression.
  • Analyzed the impact of Slug on epithelial-mesenchymal transition (EMT) markers, including E-cadherin.
  • Examined the regulation of AC007271.3 expression by the nuclear factor-κB (NF-κB) pathway.

Main Results:

  • AC007271.3 acts as a ceRNA, sequestering miR-125b-2-3p and leading to increased Slug expression.
  • Slug upregulation resulted in decreased E-cadherin expression, indicative of EMT.
  • The canonical NF-κB pathway was identified as a promoter of AC007271.3 expression.

Conclusions:

  • The NF-κB pathway-activated AC007271.3 promotes OSCC development by regulating EMT via the miR-125b-2-3p/Slug/E-cadherin axis.
  • AC007271.3 represents a novel molecular target for therapeutic interventions in oral squamous cell carcinoma.
  • Understanding this pathway provides critical insights into OSCC pathogenesis.

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