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The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating

Jiancheng Xu1, Guangchao Wang1, Wei Gong1

  • 1State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Molecular Oncology
|December 18, 2019
PubMed

Insights

NELFA mRNA interacts with Rad17 in the nucleus, impacting oesophageal squamous cell carcinoma (ESCC) progression. Its inhibition reduces ESCC proliferation and DNA repair, highlighting NELFA mRNA as a potential therapeutic target for ESCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • RNA Biology

Background:

  • Protein-RNA interactions are crucial in oesophageal squamous cell carcinoma (ESCC) development.
  • The specific role of NELFA mRNA in ESCC pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the noncoding function of NELFA mRNA in ESCC.
  • To determine the interaction of NELFA mRNA with Rad17 and its downstream effects.
  • To evaluate NELFA mRNA as a potential therapeutic target and prognostic biomarker for ESCC.

Main Methods:

  • Investigated NELFA mRNA and Rad17 interaction in the nucleus.
  • Assessed the impact of NELFA mRNA deletion and knockdown on ESCC cell proliferation, colony formation, DNA damage repair, and apoptosis.
  • Analyzed the regulation of Rad17-RFC2-5 interaction and CHK1, CHK2, BRCA1 phosphorylation.
  • Correlated NELFA mRNA expression with patient survival data.

Main Results:

  • NELFA mRNA interacts with Rad17 via a novel noncoding nuclear mechanism.
  • USF2 aberrant expression upregulates Rad17 and NELFA mRNA.
  • NELFA mRNA deletion significantly reduces ESCC proliferation and colony formation in vitro.
  • NELFA mRNA knockdown inhibits DNA damage repair and promotes apoptosis.
  • NELFA mRNA regulates Rad17-RFC2-5 interaction, impacting CHK1, CHK2, and BRCA1 phosphorylation.
  • Elevated NELFA mRNA expression in ESCC patients correlates with decreased overall survival.

Conclusions:

  • NELFA mRNA plays a critical noncoding role in ESCC tumorigenesis.
  • NELFA mRNA serves as a potential therapeutic target for ESCC.
  • NELFA mRNA is an independent prognostic indicator for ESCC patients.
Keywords:
ESCCNELFA mRNARFC2-5Rad17USF2

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