Copy number gain of hsa-miR-569 at 3q26.2 leads to loss of TP53INP1 and aggressiveness of epithelial cancers

Pradeep Chaluvally-Raghavan; Fan Zhang; Sunila Pradeep; Mark P Hamilton; Xi Zhao; Rajesha Rupaimoole; Tyler Moss; Yiling Lu; Shuangxing Yu; Chad V Pecot; Miriam R Aure; Sylvain Peuget; Cristian Rodriguez-Aguayo; Hee-Dong Han; Dong Zhang; Avinashnarayan Venkatanarayan; Marit Krohn; Vessela N Kristensen; Mihai Gagea; Prahlad Ram; Wenbin Liu; Gabriel Lopez-Berestein; Philip L Lorenzi; Anne-Lise Børresen-Dale; Koei Chin; Joe Gray; Nelson J Dusetti; Sean E McGuire; Elsa R Flores; Anil K Sood; Gordon B Mills

doi:10.1016/j.ccell.2014.10.010

Copy number gain of hsa-miR-569 at 3q26.2 leads to loss of TP53INP1 and aggressiveness of epithelial cancers

Cancer Cell. 2014 Dec 8;26(6):863-879. doi: 10.1016/j.ccell.2014.10.010.

Authors

Pradeep Chaluvally-Raghavan¹, Fan Zhang², Sunila Pradeep³, Mark P Hamilton⁴, Xi Zhao⁵, Rajesha Rupaimoole⁶, Tyler Moss², Yiling Lu², Shuangxing Yu², Chad V Pecot⁷, Miriam R Aure⁵, Sylvain Peuget⁸, Cristian Rodriguez-Aguayo⁹, Hee-Dong Han¹⁰, Dong Zhang², Avinashnarayan Venkatanarayan¹¹, Marit Krohn⁵, Vessela N Kristensen⁵, Mihai Gagea¹², Prahlad Ram², Wenbin Liu¹³, Gabriel Lopez-Berestein¹⁴, Philip L Lorenzi¹³, Anne-Lise Børresen-Dale⁵, Koei Chin¹⁵, Joe Gray¹⁵, Nelson J Dusetti⁸, Sean E McGuire¹⁶, Elsa R Flores¹¹, Anil K Sood¹⁷, Gordon B Mills¹⁸

Affiliations

¹ Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Electronic address: pcraghavan@mdanderson.org.
² Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
³ Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
⁴ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
⁵ Department of Genetics, Institute for Cancer Research, Oslo University Hospital, the Norwegian Radium Hospital, 0424 Oslo, Norway; The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0424 Oslo, Norway.
⁶ Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
⁷ Department of Thoracic, Head and Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
⁸ INSERM U1068, CRCM, Cell Stress, Marseille F-13009, France; Institut Paoli-Calmettes, 13273 Marseille Cedex 9, France; UMR7258, CNRS, Aix-Marseille University, Marseille F-13009, France.
⁹ Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
¹⁰ Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
¹¹ Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
¹² Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
¹³ Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
¹⁴ Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
¹⁵ Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
¹⁶ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁷ Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
¹⁸ Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Electronic address: gmills@mdanderson.org.

Abstract

Small noncoding miRNAs represent underexplored targets of genomic aberrations and emerging therapeutic targets. The 3q26.2 amplicon is among the most frequent genomic aberrations in multiple cancer lineages including ovarian and breast cancers. We demonstrate that hsa-miR-569 (hereafter designated as miR569), which is overexpressed in a subset of ovarian and breast cancers, at least in part due to the 3q26.2 amplicon, alters cell survival and proliferation. Downregulation of TP53INP1 expression by miR569 is required for the effects of miR569 on survival and proliferation. Targeting miR569 sensitizes ovarian and breast cancer cells overexpressing miR569 to cisplatin by increasing cell death both in vitro and in vivo. Thus targeting miR569 could potentially benefit patients with the 3q26.2 amplicon and subsequent miR569 elevation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Breast Neoplasms / genetics*
Breast Neoplasms / pathology
Carrier Proteins / metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Chromosomes, Human, Pair 3
Cisplatin / pharmacology
Female
Gene Amplification
Gene Duplication
Gene Expression Regulation, Neoplastic / drug effects
Heat-Shock Proteins / metabolism*
Humans
Mice
Mice, Nude
MicroRNAs / genetics
MicroRNAs / metabolism*
Neoplasms, Experimental
Neoplasms, Glandular and Epithelial / genetics*
Neoplasms, Glandular and Epithelial / pathology
Nuclear Proteins / metabolism*
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / pathology

Substances

Antineoplastic Agents
Carrier Proteins
Heat-Shock Proteins
MIRN-569 microRNA, human
MIRN-569 microRNA, mouse
MicroRNAs
Nuclear Proteins
TP53INP1 protein, human
tumor protein 53-induced nuclear protein 1, mouse
Cisplatin

Abstract

Publication types

MeSH terms

Substances

Grants and funding