Related Experiment Video

Updated: May 2, 2026

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

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MicroRNA-375 promotes tamoxifen resistance by stabilizing ERα via UBE3A-mediated ubiquitination

Dinglong Xue1, Yuyan Xie1, Jiayue Sun1

  • 1Department of Medical Oncology, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Harbin 150040, China.

International Immunopharmacology
|March 2, 2026
PubMed
Abstract

Insights

MicroRNA-375 (miR-375) promotes estrogen receptor-positive breast cancer progression and tamoxifen resistance by stabilizing ERα. Targeting miR-375 may offer a new strategy to overcome endocrine resistance in ER+ breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Estrogen receptor alpha (ERα) signaling is crucial in ER-positive (ER+) breast cancer and its disruption drives endocrine resistance.
  • MicroRNA-375 (miR-375) acts as a context-dependent regulator in various cancers, with its role in breast cancer progression and tamoxifen resistance needing further elucidation.

Purpose of the Study:

  • To investigate the role of miR-375 in the progression of breast cancer and the development of tamoxifen resistance.
  • To elucidate the molecular mechanisms underlying miR-375's function in ER+ breast cancer.

Main Methods:

  • Quantitative reverse transcription PCR (qRT-PCR) for miR-375 expression analysis.
  • Kaplan-Meier plotter for survival analysis.
  • In vitro and in vivo gain- and loss-of-function assays to evaluate functional roles.
  • Dual-luciferase reporter assays, immunoprecipitation (IP), immunofluorescence (IF), and ubiquitination analyses to investigate the miR-375-UBE3A-ERα axis.

Main Results:

  • miR-375 expression is significantly higher in ER+ breast cancer tissues and correlates with worse overall survival.
  • Overexpression of miR-375 enhances ERα protein stability, promoting proliferation, migration, invasion, and tamoxifen resistance while reducing apoptosis.
  • miR-375 targets UBE3A, which in turn facilitates ERα degradation via the ubiquitin-proteasome pathway.

Conclusions:

  • The miR-375-UBE3A-ERα signaling axis plays a significant role in breast cancer progression and tamoxifen resistance.
  • Targeting miR-375 presents a potential therapeutic strategy to overcome endocrine resistance in ER+ breast cancer.
Keywords:
ER(+) breast cancerTamoxifen sensitivityUbiquitinationmiRNA

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