Targeted Inhibition of RPA3 Impairs Breast Cancer Progression Through Suppressing TGF-β Signaling Pathway-Mediated

Zhiyi Zhang1, Haipeng Yu2, Liqun Hao1

  • 1Huguang Internal Medicine Ward Ⅱ, Jilin Cancer Hospital, Changchun, China.

Insights

High RPA3 expression in breast cancer predicts poor outcomes. RPA3 knockdown suppressed tumor growth by inhibiting the TGF-β pathway and blocking autophagy, suggesting RPA3 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Replication protein A (RPA) complex component RPA3 is oncogenic in several solid tumors.
  • The specific role of RPA3 in breast cancer pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the expression and prognostic significance of RPA3 in breast cancer.
  • To elucidate the biological functions and molecular mechanisms of RPA3 in breast cancer progression.

Main Methods:

  • Analysis of public databases for RPA3 expression and patient outcomes.
  • RPA3 knockdown in MCF-7 breast cancer cells.
  • In vitro assays (Cell Counting Kit-8, colony formation, Western blot, immunofluorescence, transmission electron microscopy).
  • In vivo xenograft model studies.

Main Results:

  • High RPA3 expression correlates with adverse patient outcomes in breast cancer.
  • RPA3 knockdown suppressed breast cancer cell proliferation in vitro and tumor growth in vivo.
  • RPA3 knockdown inhibited the transforming growth factor-β (TGF-β) pathway by reducing TGF-β1 expression and Smad2/3 phosphorylation.
  • RPA3 knockdown blocked autophagy, indicated by altered LC3 and p62 levels and reduced LC3 puncta.

Conclusions:

  • RPA3 plays a significant oncogenic role in breast cancer.
  • RPA3 promotes breast cancer progression via the TGF-β pathway and regulation of autophagy.
  • RPA3 represents a potential therapeutic target for breast cancer treatment.

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