lincRNA-RoR and miR-145 regulate invasion in triple-negative breast cancer via targeting ARF6

Gabriel Eades1, Benjamin Wolfson1, Yongshu Zhang1

  • 1Greenebaum Cancer Center, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland.

Abstract

Insights

Triple-negative breast cancer (TNBC) metastasis is driven by the lincRNA-RoR/miR-145/ARF6 pathway. This pathway, involving upregulated lincRNA-RoR and ARF6, and downregulated miR-145, regulates tumor cell invasion and could be a therapeutic target.

Area of Science:

  • Molecular Oncology
  • Cancer Genomics
  • RNA Biology

Background:

  • Triple-negative breast cancer (TNBC) is aggressive with poor prognosis and lacks targeted therapies.
  • MicroRNA-145 (miR-145) silencing is a potential TNBC marker.
  • Understanding miR-145 downregulation mechanisms is crucial for TNBC treatment.

Purpose of the Study:

  • To investigate the molecular mechanism of miR-145 downregulation in TNBC.
  • To identify novel therapeutic targets for TNBC metastasis.

Main Methods:

  • Molecular profiling and deep sequencing identified miR-145 silencing.
  • Overexpression of long intergenic noncoding RNA regulator of reprogramming (lincRNA-RoR) was analyzed.
  • Knockdown experiments assessed the impact on miR-145 expression.
  • Target validation identified ADP-ribosylation factor 6 (Arf6) as a miR-145 target.

Main Results:

  • lincRNA-RoR acts as a competing endogenous RNA sponge, upregulated in TNBC and metastasis.
  • Knockdown of lincRNA-RoR restored miR-145 expression.
  • miR-145 regulates TNBC cell invasion, not proliferation or apoptosis.
  • ARF6 is upregulated in TNBC and metastasis, regulating invasion and cell-cell adhesion via E-cadherin.

Conclusions:

  • A novel lincRNA-RoR/miR-145/ARF6 pathway critically regulates TNBC invasion and metastasis.
  • This pathway presents potential biomarkers and therapeutic targets for improving TNBC patient survival.

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