SNORA47 affects stemness and chemotherapy sensitivity via EBF3/RPL11/c-Myc axis in luminal A breast cancer

Qilin Han1,2, Ying Zhou1, Zixian Dong1

  • 1Department of Breast Surgery, the First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning, 110001, China.

Insights

High SNORA47 expression in Luminal A breast cancer is linked to poor survival and chemotherapy resistance. This small nucleolar RNA drives cancer stemness by regulating the c-Myc oncogene via the EBF3-RPL11 pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Chemotherapy resistance in breast cancer impacts patient prognosis.
  • Breast cancer stem cells (BCSCs) are implicated in chemotherapy resistance.
  • SNORA47, a small nucleolar RNA, is uncharacterized in breast cancer but known in lung cancer.

Purpose of the Study:

  • To investigate the role of SNORA47 in breast cancer, particularly Luminal A subtype.
  • To explore the association between SNORA47 expression and patient survival and tumor characteristics.
  • To elucidate the molecular mechanism by which SNORA47 influences breast cancer stemness and drug sensitivity.

Main Methods:

  • Analysis of SNORA47 expression in The Cancer Genome Atlas (TCGA) database for breast cancer patients.
  • Correlation analysis of SNORA47 expression with clinical parameters like TNM stage.
  • In vitro and in vivo experiments to assess the impact of SNORA47 on breast cancer stemness and tumor sensitivity.
  • Investigation of molecular interactions involving SNORA47, EBF3, RPL11, and c-Myc.

Main Results:

  • High SNORA47 expression correlated with unfavorable survival outcomes in Luminal A breast cancer patients.
  • Elevated SNORA47 levels were associated with advanced TNM stage in Luminal A breast cancer.
  • SNORA47 demonstrated a strong link to breast cancer stemness and tumor sensitivity both in vitro and in vivo.
  • SNORA47 facilitates c-Myc regulation by interacting with EBF3 and influencing RPL11 translocation.

Conclusions:

  • SNORA47 is a potential biomarker for poor prognosis in Luminal A breast cancer.
  • The SNORA47-EBF3-RPL11 axis plays a critical role in regulating c-Myc and promoting breast cancer stemness.
  • Targeting the SNORA47 pathway offers a potential therapeutic strategy to overcome chemotherapy resistance in breast cancer.

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