Phosphodiesterase 7b/microrna-200c relationship regulates triple-negative breast cancer cell growth

ABSTRACT Members of microRNA-200 (miRNA-200) family have a regulatory role in epithelial to mesenchymal transition (EMT) by suppressing Zeb1 and Zeb2 expression. Consistent with its role in

suppressing EMT, Hsa-miR-200c-3p (miR-200c), a member of miR-200 family is poorly expressed in mesenchymal-like triple-negative breast cancer (TNBC) cells and ectopic miR-200c expression

suppresses cell migration. In this study, we demonstrated that miR-200c potently inhibited TNBC cell growth and tumor development in a mechanism distinct from its ability to downregulate

Zeb1 and Zeb2 expression, because silencing them only marginally affected TNBC cell growth. We identified phosphodiesterase 7B (PDE7B) as a bona fide miR-200c target. Importantly,

miR-200c-led inhibition in cell growth and tumor development was prevented by forcing PDE7B transgene expression, while knockdown of PDE7B effectively inhibited cell growth. These results

suggest that miR-200c inhibits cell growth by targeting PDE7B mRNA. To elucidate mechanism underlying miR-200c/PDE7B regulation of TNBC cell growth, we showed that cAMP concentration was

lower in TNBC cells compared with estrogen receptor-positive (ER + ) cells, and that both miR-200c and PDE7B siRNAs were able to increase cAMP concentration in TNBC cells. High level of

cellular cAMP has been shown to induce cell cycle arrest and apoptosis in TNBC cells. Our observation that ectopic expression of miR-200c triggered apoptosis indicates that it does so by

elevating level of cellular cAMP. Analysis of breast tumor gene expression datasets revealed an inverse association between miR-200c and PDE7B expression. Especially, both low miR-200c and

high PDE7B expression were correlated with poor survival of breast cancer patients. Our study supports a critical role of miR-200c/PDE7B relationship in TNBC tumorigenesis. Access through

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BEING VIEWED BY OTHERS MICRORNA-203A INHIBITS BREAST CANCER PROGRESSION THROUGH THE PI3K/AKT AND WNT PATHWAYS Article Open access 27 February 2024 SILENCING TRAIP SUPPRESSES CELL

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This work was supported by funding from NSF of China 81773946, 81573673, 81001666 (DZ), NIH CA187152 (SH), and Florida Breast Cancer Foundation (SH). AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Institute of Interdisciplinary Integrative Medical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China Dan-Dan Zhang, Yuan Xu & Shuang

Huang * Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL, 32608, USA Yue Li & Shuang Huang * Department of Statistics, Sungkyunkwan

University, Seoul, 03063, South Korea Jaejik Kim Authors * Dan-Dan Zhang View author publications You can also search for this author inPubMed Google Scholar * Yue Li View author

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author publications You can also search for this author inPubMed Google Scholar * Shuang Huang View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHORS Correspondence to Dan-Dan Zhang or Shuang Huang. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of interest. ELECTRONIC

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7B/microRNA-200c relationship regulates triple-negative breast cancer cell growth. _Oncogene_ 38, 1106–1120 (2019). https://doi.org/10.1038/s41388-018-0499-2 Download citation * Received: 07

February 2018 * Revised: 27 July 2018 * Accepted: 31 July 2018 * Published: 12 September 2018 * Issue Date: 14 February 2019 * DOI: https://doi.org/10.1038/s41388-018-0499-2 SHARE THIS

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