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Updated: Jun 13, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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LncRNA XIST/miR-455-3p/HOXC4 axis promotes breast cancer development by activating TGF-β/SMAD signaling pathway

Shanshan Zhao1, Chen Song1, Fengxi Chen1

  • 1Department of Oncology, The Second Hospital of Dalian Medical University, No.467 Zhongshan Road, Shahekou District, Dalian City, Liaoning Province, China.

Functional & Integrative Genomics
|September 11, 2024
PubMed

Insights

Long non-coding RNA XIST promotes breast cancer by regulating miR-455-3p and HOXC4. This interaction activates the TGF-β/SMAD pathway, driving tumor growth and progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Breast cancer is a leading cause of cancer death in women.
  • Abnormal expression of long non-coding RNA XIST (X-inactive specific transcript) is a hallmark of breast cancer.
  • The precise mechanism of XIST's role in breast cancer remains incompletely understood.

Purpose of the Study:

  • To elucidate the mechanism by which XIST influences breast cancer progression.
  • To investigate the regulatory network involving XIST, microRNA-455-3p (miR-455-3p), and homeobox C4 (HOXC4) in breast cancer.
  • To determine the role of this network in activating the TGF-β/SMAD pathway.

Main Methods:

  • Quantitative real-time PCR and Western blot to assess gene and protein expression.
  • Cellular assays (CCK-8, colony formation, flow cytometry, Transwell, cell scratch) to evaluate cell proliferation, invasion, migration, and cell cycle.
  • Dual-luciferase reporter assay and database analysis to validate molecular interactions.
  • In vivo tumor xenograft models to assess tumorigenic potential.

Main Results:

  • XIST and HOXC4 expression were elevated, while miR-455-3p expression was reduced in breast cancer tissues and cells.
  • XIST knockdown inhibited breast cancer cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT), inducing G0/G1 cell cycle arrest.
  • XIST directly targets miR-455-3p, which in turn targets HOXC4, forming a regulatory axis that activates the TGF-β/SMAD pathway.
  • In vivo studies confirmed that XIST knockdown suppressed tumor growth and decreased HOXC4 and p-SMAD3 expression.

Conclusions:

  • The XIST/miR-455-3p/HOXC4 axis plays a crucial role in promoting breast cancer development and progression.
  • This axis facilitates breast cancer tumorigenesis by activating the TGF-β/SMAD signaling pathway.
  • Targeting the XIST/miR-455-3p/HOXC4 pathway may offer a potential therapeutic strategy for breast cancer.
Keywords:
Breast cancerHOXC4LncRNA XISTTGF-β/SMADmiR-455-3p

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