Oncotarget

Research Papers:

microRNA-7 as a tumor suppressor and novel therapeutic for adrenocortical carcinoma

Anthony R Glover _, Jing Ting Zhao, Anthony J Gill, Jocelyn Weiss, Nancy Mugridge, Edward Kim, Alex L Feeney, Julian C Ip, Glen Reid, Stephen Clarke, Patsy S H Soon, Bruce G Robinson, Himanshu Brahmbhatt, Jennifer A. MacDiarmid, Stan B Sidhu

PDF |  HTML  |  Supplementary Files  |  Author Information  |  Order a Reprint

Oncotarget. 2015; 6:36675-36688. https://doi.org/10.18632/oncotarget.5383

Metrics: PDF 557 views  |   HTML 285 views  |   ?  


Abstract

Anthony R. Glover1,2,9,*, Jing Ting Zhao1,2,*, Anthony J. Gill2,3, Jocelyn Weiss4, Nancy Mugridge4, Edward Kim1,2, Alex L. Feeney1,2, Julian C. Ip1,2, Glen Reid5, Stephen Clarke2,6, Patsy S.H. Soon7, Bruce G. Robinson1,2,8, Himanshu Brahmbhatt4, Jennifer A. MacDiarmid4, Stan B. Sidhu1,2,9

1Cancer Genetics Laboratory, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia

2Sydney Medical School Northern, Royal North Shore Hospital, University of Sydney, St Leonards, Sydney, NSW, Australia

3Department of Anatomical Pathology, Royal North Shore Hospital and University of Sydney, St Leonards, Sydney, NSW, Australia

4EnGeneIC Ltd, Lane Cove West, Sydney, NSW, Australia

5Asbestos Diseases Research Institute, University of Sydney, Concord, Sydney, NSW, Australia

6Department of Oncology, Royal North Shore Hospital and University of Sydney, St Leonards, Sydney, NSW, Australia

7Ingham Institute for Applied Medical Research, University of New South Wales, Liverpool, NSW, Australia

8Department of Endocrinology, Royal North Shore Hospital and University of Sydney, St Leonards, Sydney, NSW, Australia

9University of Sydney Endocrine Surgery Unit, Royal North Shore Hospital, Sydney, St Leonards, Sydney, NSW, Australia

*These authors have contributed equally to this work

Correspondence to:

Stan B. Sidhu, e-mail: stanley.sidhu@sydney.edu.au

Keywords: noncoding RNA, miR-7, nanoparticle therapy, adrenal cancer

Received: July 12, 2015     Accepted: September 18, 2015     Published: October 01, 2015

ABSTRACT

Adrenocortical carcinoma (ACC) has a poor prognosis with significant unmet clinical need due to late diagnosis, high rates of recurrence/metastasis and poor response to conventional treatment. Replacing tumor suppressor microRNAs (miRNAs) offer a novel therapy, however systemic delivery remains challenging. A number of miRNAs have been described to be under-expressed in ACC however it is not known if they form a part of ACC pathogenesis. Here we report that microRNA-7–5p (miR-7) reduces cell proliferation in vitro and induces G1 cell cycle arrest. Systemic miR-7 administration in a targeted, clinically safe delivery vesicle (EGFREDVTM nanocells) reduces ACC xenograft growth originating from both ACC cell lines and primary ACC cells. Mechanistically, miR-7 targets Raf-1 proto-oncogene serine/threonine kinase (RAF1) and mechanistic target of rapamycin (MTOR). Additionally, miR-7 therapy in vivo leads to inhibition of cyclin dependent kinase 1 (CDK1). In patient ACC samples, CDK1 is overexpressed and miR-7 expression inversely related. In summary, miR-7 inhibits multiple oncogenic pathways and reduces ACC growth when systemically delivered using EDVTM nanoparticles. This data is the first study in ACC investigating the possibility of miRNAs replacement as a novel therapy.

Author Information

Anthony R Glover
Primary Contact  _

Jing Ting Zhao

Anthony J Gill

Jocelyn Weiss

Nancy Mugridge

Edward Kim

Alex L Feeney

Julian C Ip

Glen Reid

Stephen Clarke

Patsy S H Soon

Bruce G Robinson

Himanshu Brahmbhatt

Jennifer A. MacDiarmid

Stan B Sidhu


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 5383