ΔNp63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer

Marco Napoli; Avinashnarayan Venkatanarayan; Payal Raulji; Brooke A. Meyers; William Norton; Lingegowda S. Mangala; Anil K. Sood; Cristian Rodriguez-Aguayo; Gabriel Lopez-Berestein; Harina Vin; Madeleine Duvic; Michael B. Tetzlaff; Jonathan L. Curry; Alain H. Rook; Hussein A. Abbas; Cristian Coarfa; Preethi H. Gunaratne; Kenneth Y. Tsai; Elsa R. Flores

doi:10.1016/j.ccell.2016.04.016

ΔNp63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer

Marco Napoli, Avinashnarayan Venkatanarayan, Payal Raulji, Brooke A. Meyers, William Norton, Lingegowda S. Mangala, Anil K. Sood, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Harina Vin, Madeleine Duvic, Michael B. Tetzlaff, Jonathan L. Curry, Alain H. Rook, Hussein A. Abbas, Cristian Coarfa, Preethi H. Gunaratne, Kenneth Y. Tsai, Elsa R. Flores

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

ΔNp63 is an oncogenic member of the p53 family and acts to inhibit the tumor-suppressive activities of the p53 family. By performing a chemical library screen, we identified histone deacetylase inhibitors (HDACi) as agents reducing ΔNp63 protein stability through the E3 ubiquitin ligase, Fbw7. ΔNp63 inhibition decreases the levels of its transcriptional target, DGCR8, and the maturation of let-7d and miR-128, which we found to be critical for HDACi function in vitro and in vivo. Our work identified Fbw7 as a predictive marker for HDACi response in squamous cell carcinomas and lymphomas, and unveiled let-7d and miR-128 as specific targets to bypass tumor resistance to HDACi treatment.

Original language	English (US)
Pages (from-to)	874-888
Number of pages	15
Journal	Cancer cell
Volume	29
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2016.04.016
State	Published - Jun 13 2016

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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Napoli, M., Venkatanarayan, A., Raulji, P., Meyers, B. A., Norton, W., Mangala, L. S., Sood, A. K., Rodriguez-Aguayo, C., Lopez-Berestein, G., Vin, H., Duvic, M., Tetzlaff, M. B., Curry, J. L., Rook, A. H., Abbas, H. A., Coarfa, C., Gunaratne, P. H., Tsai, K. Y., & Flores, E. R. (2016). ΔNp63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer. Cancer cell, 29(6), 874-888. https://doi.org/10.1016/j.ccell.2016.04.016

Napoli, M, Venkatanarayan, A, Raulji, P, Meyers, BA, Norton, W , Mangala, LS , Sood, AK , Rodriguez-Aguayo, C , Lopez-Berestein, G, Vin, H, Duvic, M, Tetzlaff, MB, Curry, JL, Rook, AH, Abbas, HA, Coarfa, C, Gunaratne, PH, Tsai, KY & Flores, ER 2016, 'ΔNp63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer', Cancer cell, vol. 29, no. 6, pp. 874-888. https://doi.org/10.1016/j.ccell.2016.04.016

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title = "ΔNp63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer",

abstract = "ΔNp63 is an oncogenic member of the p53 family and acts to inhibit the tumor-suppressive activities of the p53 family. By performing a chemical library screen, we identified histone deacetylase inhibitors (HDACi) as agents reducing ΔNp63 protein stability through the E3 ubiquitin ligase, Fbw7. ΔNp63 inhibition decreases the levels of its transcriptional target, DGCR8, and the maturation of let-7d and miR-128, which we found to be critical for HDACi function in vitro and in vivo. Our work identified Fbw7 as a predictive marker for HDACi response in squamous cell carcinomas and lymphomas, and unveiled let-7d and miR-128 as specific targets to bypass tumor resistance to HDACi treatment.",

author = "Marco Napoli and Avinashnarayan Venkatanarayan and Payal Raulji and Meyers, {Brooke A.} and William Norton and Mangala, {Lingegowda S.} and Sood, {Anil K.} and Cristian Rodriguez-Aguayo and Gabriel Lopez-Berestein and Harina Vin and Madeleine Duvic and Tetzlaff, {Michael B.} and Curry, {Jonathan L.} and Rook, {Alain H.} and Abbas, {Hussein A.} and Cristian Coarfa and Gunaratne, {Preethi H.} and Tsai, {Kenneth Y.} and Flores, {Elsa R.}",

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year = "2016",

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doi = "10.1016/j.ccell.2016.04.016",

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AU - Napoli, Marco

AU - Venkatanarayan, Avinashnarayan

AU - Raulji, Payal

AU - Meyers, Brooke A.

AU - Norton, William

AU - Mangala, Lingegowda S.

AU - Sood, Anil K.

AU - Rodriguez-Aguayo, Cristian

AU - Lopez-Berestein, Gabriel

AU - Vin, Harina

AU - Duvic, Madeleine

AU - Tetzlaff, Michael B.

AU - Curry, Jonathan L.

AU - Rook, Alain H.

AU - Abbas, Hussein A.

AU - Coarfa, Cristian

AU - Gunaratne, Preethi H.

AU - Tsai, Kenneth Y.

AU - Flores, Elsa R.

PY - 2016/6/13

Y1 - 2016/6/13

N2 - ΔNp63 is an oncogenic member of the p53 family and acts to inhibit the tumor-suppressive activities of the p53 family. By performing a chemical library screen, we identified histone deacetylase inhibitors (HDACi) as agents reducing ΔNp63 protein stability through the E3 ubiquitin ligase, Fbw7. ΔNp63 inhibition decreases the levels of its transcriptional target, DGCR8, and the maturation of let-7d and miR-128, which we found to be critical for HDACi function in vitro and in vivo. Our work identified Fbw7 as a predictive marker for HDACi response in squamous cell carcinomas and lymphomas, and unveiled let-7d and miR-128 as specific targets to bypass tumor resistance to HDACi treatment.

AB - ΔNp63 is an oncogenic member of the p53 family and acts to inhibit the tumor-suppressive activities of the p53 family. By performing a chemical library screen, we identified histone deacetylase inhibitors (HDACi) as agents reducing ΔNp63 protein stability through the E3 ubiquitin ligase, Fbw7. ΔNp63 inhibition decreases the levels of its transcriptional target, DGCR8, and the maturation of let-7d and miR-128, which we found to be critical for HDACi function in vitro and in vivo. Our work identified Fbw7 as a predictive marker for HDACi response in squamous cell carcinomas and lymphomas, and unveiled let-7d and miR-128 as specific targets to bypass tumor resistance to HDACi treatment.

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ΔNp63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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