Related Experiment Video
Updated: Oct 29, 2025
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
miR-125a-5p impairs the metastatic potential in breast cancer via IP6K1 targeting
Mirko Minini1, Alice Senni1, Xingkang He2
1Department of Experimental Medicine, Sapienza University of Rome, 00161, Rome, Italy; Department of Surgery 'P. Valdoni', Sapienza University of Rome, 00161, Rome, Italy.
Abstract:
The deregulation of PI3K/Akt signaling is among the most causes in inducing the acquisition of a metastatic phenotype in breast cancer cells, leading to Epithelial-Mesenchymal Transition (EMT). Inhibition of the PI3K/Akt pathway is known to be beneficial in the clinical setting. However, the activation of secondary pathways and toxicity profiles of available inhibitors, hindering optimal therapeutic results. Preliminary studies showed that myo-Inositol inhibits the PI3K/Akt pathway by exerting a pleiotropic anti-tumor action. Herein, we demonstrate that myo-Inositol triggers a prompt and profound remodeling of delineated expression pattern in triple-negative breast cancer cells (MDA-MB-231). Consequently, it inhibits metastasis and tumor progression through miR-125a-5p transcription and the subsequent inhibition of IP6K1. In contrast, hormone-responsive breast cancer cells (MCF-7) are insensitive to myo-Inositol. This is due to the persistence of MDM2 synthesis promoted by estrogen-dependent pathways. Conversely, the counteraction of estrogen effects recovered the sensitivity to myo-Inositol in the hormone-responsive model. Overall, these results identify a novel axis primed by miR-125a-5p to downregulate IP6K1 gene that inhibits metastasis. Thus, administration of myo-Inositol can activate this axis as a molecular target therapy in breast cancer.
Insights
Myo-inositol inhibits breast cancer metastasis by activating miR-125a-5p, which downregulates IP6K1. This pathway is effective in triple-negative breast cancer but not hormone-responsive types unless estrogen
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Deregulation of PI3K/Akt signaling drives breast cancer metastasis via Epithelial-Mesenchymal Transition (EMT).
- Existing PI3K/Akt inhibitors face challenges like secondary pathway activation and toxicity.
- Myo-inositol shows preliminary potential for PI3K/Akt pathway inhibition and anti-tumor effects.
Purpose of the Study:
- To investigate the anti-metastatic effects of myo-inositol in breast cancer.
- To elucidate the molecular mechanisms underlying myo-inositol's action.
- To determine the differential response of breast cancer subtypes to myo-inositol.
Main Methods:
- Treatment of triple-negative (MDA-MB-231) and hormone-responsive (MCF-7) breast cancer cells with myo-inositol.
- Analysis of gene and microRNA expression patterns.
- Assessment of metastasis and tumor progression markers.
- Investigation of estrogen's role in myo-inositol sensitivity.
Main Results:
- Myo-inositol induced significant changes in gene expression and inhibited metastasis in triple-negative breast cancer cells.
- This effect was mediated by the transcription of miR-125a-5p, leading to the inhibition of IP6K1.
- Hormone-responsive cells showed insensitivity due to estrogen-dependent MDM2 synthesis, which was reversed upon blocking estrogen effects.
Conclusions:
- Myo-inositol activates a novel miR-125a-5p/IP6K1 axis to suppress breast cancer metastasis.
- This pathway represents a potential molecular target for breast cancer therapy, particularly in triple-negative subtypes.
- Estrogen signaling modulates sensitivity to myo-inositol in hormone-responsive breast cancer.
Related Concept Videos
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
01:22MicroRNAs