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Restoring Tamoxifen Sensitivity in Breast Cancer: The Role of lncRNA MALAT1 and NanoCurcumin as Modulators of Drug

Fatemeh Nasiri Kenari1, Masoumeh Saberian2, Matthew Abikenari3

  • 1Department of Molecular Genetics, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran, modares.ac.ir.

Biomed Research International
|October 1, 2025
PubMed

Insights

NanoCurcumin, combined with tamoxifen, combats estrogen receptor-positive breast cancer resistance by reducing MALAT1 long noncoding RNA levels. This epigenetic strategy enhances endocrine therapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Estrogen receptor-positive (ER+) breast cancer often develops tamoxifen resistance, leading to poor patient outcomes.
  • Long noncoding RNAs (lncRNAs) like MALAT1 are implicated in endocrine resistance mechanisms.
  • Curcumin, particularly its bioavailable NanoCurcumin formulation, shows potential in modulating lncRNA expression and enhancing cancer therapy.

Purpose of the Study:

  • To investigate the combined effects of NanoCurcumin and tamoxifen on lncRNA expression in ER+ breast cancer.
  • To evaluate NanoCurcumin's role in overcoming tamoxifen resistance by targeting MALAT1.
  • To explore a novel epigenetic approach for improving endocrine therapy efficacy.

Main Methods:

  • Assessed plasma lncRNA levels (MALAT1, UCA1, CYTOR, GAS5, HOTAIR) using qRT-PCR in patients receiving tamoxifen with or without NanoCurcumin.
  • Utilized bioinformatics analysis of the GEO database for MALAT1 expression in tamoxifen-resistant cell lines.
  • In vitro studies involved evaluating MALAT1 expression in breast cancer cell lines (MCF7) and tamoxifen-resistant MCF7 models treated with NanoCurcumin.

Main Results:

  • NanoCurcumin significantly downregulated MALAT1 in clinical samples (p=0.02) and tended to decrease other lncRNAs while increasing GAS5.
  • Bioinformatics and in vitro analyses confirmed MALAT1 upregulation in tamoxifen-resistant breast cancer cells.
  • NanoCurcumin treatment reversed MALAT1 upregulation in vitro, mitigating tamoxifen resistance.

Conclusions:

  • NanoCurcumin demonstrates potential in mitigating tamoxifen resistance in ER+ breast cancer by downregulating MALAT1.
  • This suggests a novel epigenetic strategy to enhance the efficacy of endocrine therapy.
  • Further research into lncRNA-targeted interventions is warranted to improve treatment outcomes for ER+ breast cancer patients.
Keywords:
NanoCurcuminbreast cancerlncRNA MALAT1plasma biomarkertamoxifen resistance

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