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Regulation of miR-19 to Breast Cancer Chemoresistance Through Targeting PTEN

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An Editorial Expression of Concern to this article was published on 28 October 2022

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ABSTRACT

Purpose

To explore whether miR-19 is involved in the regulation of multidrug resistance (MDR), one of the main causes of breast cancer mortality, and modulates sensitivity of tumor cells to chemotherapeutic agents.

Methods

We analyzed miRNA expression levels in three MDR cell lines in comparison with their parent cell line, MCF-7, using a miRNA microarray. We investigated whether inhibitor of miR-19 sensitized MDR cells to chemotherapeutic agents in vitro and in vivo.

Results

MiR-19 was overexpressed in all three MDR cell lines compared to their parental cell line, MCF-7. Expression levels of miR-19 in MDR cells were inversely consistent with those of PTEN. Inhibitor of miR-19a restored sensitivity of MDR cells to cytotoxic agents; administration of LNA-antimiR-19a, a chemo-modified miR-19a inhibitor, sensitized MDR cells to chemotherapeutic agents in vivo.

Conclusion

Our findings demonstrate, for the first time, involvement of miR-19 in multidrug resistance through modulation of PTEN and suggest that miR-19 may be a potential target for preventing and reversing MDR in tumor cells.

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Abbreviations

BCRP:

breast cancer resistance protein

LNA:

locked nucleic acid

MDR:

multidrug resistance

MDR-1:

multidrug resistance 1

miRNA:

microRNA

MRP-1:

multidrug resistance-associated protein 1

PTEN:

phosphatase and tensin homolog

RT-PCR:

reverse transcription polymerase chain reaction.

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ACKNOWLEDGMENTS & DISCLOSURES

This study was financially supported by the Department of Defense Breast Cancer Program Concept Award (BC052118) to ZL as well as a Research Grant from NIH NCI (1R01CA109366) to HS. We thank Dr. Susan E. Bates from NCI/NIH, Bethesda, MD for her valuable advice. We acknowledge James Xia and Robert Craig Castellino for technical help. The authors thank Ms. Jessica Paulishen for proof-reading.

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Authors and Affiliations

  1. Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia, 30322, USA

    Zhongxing Liang, Ke Huang & Hyunsuk Shim

  2. Winship Cancer Institute, Emory University, Atlanta, Georgia, 30322, USA

    Zhongxing Liang & Hyunsuk Shim

  3. Yerkes Microarray Core, Yerkes National Primate Research Center Emory University, Atlanta, Georgia, 30322, USA

    Yuhua Li & Nicholas Wagar

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  1. Zhongxing Liang
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  2. Yuhua Li
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  3. Ke Huang
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Correspondence to Zhongxing Liang or Hyunsuk Shim.

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Liang, Z., Li, Y., Huang, K. et al. Regulation of miR-19 to Breast Cancer Chemoresistance Through Targeting PTEN. Pharm Res 28, 3091–3100 (2011). https://doi.org/10.1007/s11095-011-0570-y

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  • DOI: https://doi.org/10.1007/s11095-011-0570-y

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