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Long non-coding antisense RNA HYOU1-AS is essential to human breast cancer development through competitive binding

Aixin Hao1, Yu Wang1, Xiao Zhang1

  • 1Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin 150040, China.

Biochimica Et Biophysica Acta. Molecular Cell Research
|January 10, 2021
PubMed

Insights

Triple negative breast cancer (TNBC) progression is promoted by the long noncoding RNA HYOU1-AS. This lncRNA upregulates the HYOU1 gene, impacting cell proliferation and migration, and is linked to poor patient outcomes.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Triple negative breast cancer (TNBC) presents a poor prognosis due to a lack of effective biomarkers and therapeutic targets.
  • Long noncoding RNAs (lncRNAs) are increasingly implicated in cancer progression, but their specific roles in TNBC remain largely uncharacterized.
  • Understanding lncRNA functions is crucial for developing novel therapeutic strategies against TNBC.

Purpose of the Study:

  • To identify novel lncRNAs involved in TNBC pathogenesis.
  • To elucidate the functional role and regulatory mechanism of a specific lncRNA, HYOU1-AS, in TNBC.
  • To investigate the correlation between HYOU1-AS, its target gene HYOU1, and clinical outcomes in breast cancer patients.

Main Methods:

  • lncRNA microarray analysis was performed on TNBC samples and matched normal tissues.
  • HYOU1-AS expression and localization were analyzed in TNBC cells.
  • Functional assays included HYOU1-AS knockdown in TNBC cells, xenograft tumor formation studies in nude mice, and mechanistic studies involving RNA-binding proteins.
  • TCGA database analysis was used to correlate HYOU1 levels with patient outcomes.

Main Results:

  • A novel antisense lncRNA, HYOU1-AS, was identified and found to be highly expressed in the nucleus of TNBC cells.
  • Knockdown of HYOU1-AS inhibited TNBC cell proliferation, migration, and xenograft tumor growth.
  • HYOU1-AS was shown to promote HYOU1 expression by competitively binding to hnRNPA1, thereby relieving post-transcriptional inhibition.
  • Elevated HYOU1 levels correlated with poorer clinical outcomes in breast cancer patients.

Conclusions:

  • The lncRNA HYOU1-AS acts as a driver of TNBC progression by upregulating the proliferative gene HYOU1.
  • HYOU1-AS represents a potential diagnostic biomarker and therapeutic target for triple negative breast cancer.
  • Targeting the HYOU1-AS/hnRNPA1/HYOU1 axis may offer a novel therapeutic strategy for TNBC treatment.
Keywords:
HYOU1-ASHypoxia up-regulated 1 (HYOU1)TNBChnRNPA1lncRNA

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