The isomiR-140-3p-regulated mevalonic acid pathway as a potential target for prevention of triple negative breast cancer View Full Text


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Article Info

DATE

2018-12

AUTHORS

Anjana Bhardwaj, Harpreet Singh, Celestine Marie Trinidad, Constance T. Albarracin, Kelly K. Hunt, Isabelle Bedrosian

ABSTRACT

BACKGROUND: Prevention of triple-negative breast cancer (TNBC) is hampered by lack of knowledge about the drivers of tumorigenesis. METHODS: To identify molecular markers and their downstream networks that can potentially be targeted for TNBC prevention, we analyzed small RNA and RNA sequencing of a cell line model that represent early stages of TNBC development. We have identified direct gene targets of isomiRNA-140-3p and by using cell-based and in vivo model systems we have demonstrated the utility of targeting downstream pathways for prevention of TNBC. RESULTS: These analyses showed that 5'isomiRNA of miR-140-3p (miR-140-3p-1) and its novel direct gene targets, HMG-CoA reductase (HMGCR) and HMG-CoA synthase 1(HMGCS1), key enzymes in the cholesterol biosynthesis pathway, were deregulated in the normal-to-preneoplastic transition. Upregulation in the cholesterol pathway creates metabolic vulnerability that can be targeted. Consistent with this hypothesis, we found direct targeting of miR-140-3p-1 and its downstream pathway by fluvastatin to inhibit growth of these preneoplastic MCF10.AT1 cells. However, although, fluvastatin inhibited the growth of MCF10.AT1-derived xenografts, histological progression remained unchanged. The cholesterol pathway is highly regulated, and HMGCR enzymatic activity inhibition is known to trigger a feedback response leading to restoration of the pathway. Indeed, we found fluvastatin-induced HMGCR transcript levels to be directly correlated with the degree of histological progression of lesions, indicating that the extent of cholesterol pathway suppression directly correlates with abrogation of the tumorigenic process. To block the HMGCR feedback response to statins, we treated resistant preneoplastic cells with an activator of AMP-activated protein kinase (AMPK), a brake in the cholesterol feedback pathway. AMPK activation by aspirin and metformin effectively abrogated the statin-induced aberrant upregulation of HMGCR and sensitized these resistant cells to fluvastatin. CONCLUSIONS: These results suggest the potential use of combined treatment with statin and aspirin for prevention of TNBC. More... »

PAGES

150

References to SciGraph publications

  • 2016-12. The highly expressed 5’isomiR of hsa-miR-140-3p contributes to the tumor-suppressive effects of miR-140 by reducing breast cancer proliferation and migration in BMC GENOMICS
  • 2016-11. Targeting mutant p53 through the mevalonate pathway in NATURE CELL BIOLOGY
  • 2000-10. Xenograft Models of Premalignant Breast Disease in JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
  • 2016-11. The interplay between cell signalling and the mevalonate pathway in cancer in NATURE REVIEWS CANCER
  • 2001-01. Tamoxifen Suppresses Histologic Progression to Atypia and DCIS in MCFIOAT Xenografts, a Model of Early Human Breast Cancer in BREAST CANCER RESEARCH AND TREATMENT
  • 2015-12. Statin-induced anti-proliferative effects via cyclin D1 and p27 in a window-of-opportunity breast cancer trial in JOURNAL OF TRANSLATIONAL MEDICINE
  • 2016-07. Phase I biomarker modulation study of atorvastatin in women at increased risk for breast cancer in BREAST CANCER RESEARCH AND TREATMENT
  • 2012-02. A short-term biomarker modulation study of simvastatin in women at increased risk of a new breast cancer in BREAST CANCER RESEARCH AND TREATMENT
  • 2011-12. MicroRNAs and their isomiRs function cooperatively to target common biological pathways in GENOME BIOLOGY
  • 2016-11. DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway in NATURE CELL BIOLOGY
  • 2013-11. A clinical trial of lovastatin for modification of biomarkers associated with breast cancer risk in BREAST CANCER RESEARCH AND TREATMENT
  • 2014-12. Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion in JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
  • Identifiers

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    http://scigraph.springernature.com/pub.10.1186/s13058-018-1074-z

    DOI

    http://dx.doi.org/10.1186/s13058-018-1074-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1110542092

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30537987


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