Oncotarget

Research Papers:

Functional and prognostic significance of long non-coding RNA MALAT1 as a metastasis driver in ER negative lymph node negative breast cancer

Mahdieh Jadaliha _, Xinying Zong, Pushkar Malakar, Tania Ray, Deepak K. Singh, Susan M. Freier, Tor Jensen, Supriya G. Prasanth, Rotem Karni, Partha S. Ray and Kannanganattu V. Prasanth

PDF  |  HTML  |  Supplementary Files  |  Order a Reprint

Oncotarget. 2016; 7:40418-40436. https://doi.org/10.18632/oncotarget.9622

Metrics: PDF 1556 views  |   HTML 1301 views  |   ?  


Abstract

Mahdieh Jadaliha1, Xinying Zong1, Pushkar Malakar2, Tania Ray3, Deepak K. Singh1, Susan M. Freier4, Tor Jensen5, Supriya G. Prasanth1, Rotem Karni2, Partha S. Ray6,7, Kannanganattu V. Prasanth1

1Department of Cell and Developmental Biology, University of Illinois, Urbana, IL, USA

2Department of Biochemistry and Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel

3Onconostic Technologies, Champaign, IL, USA

4Ionis Pharmaceuticals Inc., Carlsbad, CA, USA

5Interdisciplinary Health Sciences Initiative, University of Illinois, Urbana, IL, USA

6Department of Surgery, University of Illinois College of Medicine, Champaign, IL, USA

7Carle Cancer Center, Urbana, IL, USA

Correspondence to:

Kannanganattu V. Prasanth, email: kumarp@illinois.edu

Partha S. Ray, email: psray@illinois.edu

Rotem Karni, email: rotemka@ekmd.huji.ac.il

Keywords: breast cancer, nuclear speckle, triple negative breast cancer, lncRNA, basal-like breast cancer cells

Received: February 05, 2016    Accepted: May 09, 2016    Published: May 26, 2016

ABSTRACT

MALAT1 (metastasis associated lung adenocarcinoma transcript1) is a conserved long non-coding RNA, known to regulate gene expression by modulating transcription and post-transcriptional pre-mRNA processing of a large number of genes. MALAT1 expression is deregulated in various tumors, including breast cancer. However, the significance of such abnormal expression is yet to be fully understood. In this study, we demonstrate that regulation of aggressive breast cancer cell traits by MALAT1 is not predicted solely based on an elevated expression level but is context specific. By performing loss- and gain-of-function studies, both under in vitro and in vivo conditions, we demonstrate that MALAT1 facilitates cell proliferation, tumor progression and metastasis of triple-negative breast cancer (TNBC) cells despite having a comparatively lower expression level than ER or HER2-positive breast cancer cells. Furthermore, MALAT1 regulates the expression of several cancer metastasis-related genes, but displays molecular subtype specific correlations with such genes. Assessment of the prognostic significance of MALAT1 in human breast cancer (n=1992) revealed elevated MALAT1 expression was associated with decreased disease-specific survival in ER negative, lymph node negative patients of the HER2 and TNBC molecular subtypes. Multivariable analysis confirmed MALAT1 to have independent prognostic significance in the TNBC lymph node negative patient subset (HR=2.64, 95%CI 1.35- 5.16, p=0.005). We propose that the functional significance of MALAT1 as a metastasis driver and its potential use as a prognostic marker is most promising for those patients diagnosed with ER negative, lymph node negative breast cancer who might otherwise mistakenly be stratified to have low recurrence risk.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 9622