Elsevier

Biomedicine & Pharmacotherapy

Volume 69, February 2015, Pages 221-227
Biomedicine & Pharmacotherapy

Original article
Microarray expression profile analysis of long non-coding RNAs in human breast cancer: A study of Chinese women

https://doi.org/10.1016/j.biopha.2014.12.002Get rights and content

Abstract

Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer death among women. Long non-coding RNAs (lncRNAs) are key regulators of gene expression. Numerous lncRNAs have performed critical roles in cancer biology including breast cancer (BC). The expression levels of certain lncRNAs are associated with tumor development, recurrence, metastasis, and prognosis. However, the potential roles that lncRNAs regulate breast cancer tumorigenesis and tumor progression are still poorly understood. To investigate the potential roles of lncRNAs in the breast cancer, we constructed BC related lncRNA libraries by using microarray. Microarray expression profiling suggests 790 up-regulated and 637 down-regulated (log fold-change > 2.3) lncRNAs were differently expressed between BC tissues and its paired adjacent tissues. Furthermore, we found differently expressed lncRNAs associated with immune regulation. RP4-583P15.10, an up-regulated lncRNA, was found to be located downstream of the natural antisense of the ZBTB46 gene, which may regulated breast cancer through influence immune system. In conclusion, our results for the first time indicate that distinct lncRNAs expression profiles of BC, which related to the immune network, may provide information for further research on immune regulation during the BC process.

Introduction

Breast cancer (BC) is the most common type of tumor in women. The incidence of breast cancer in western countries has decreased or at least been stable over the last few decades, but the incidence is increasing in China and in many developing countries [1]. The potential mechanisms that regulate breast cancer progression are still poorly understood. The development of BC is a complex multistep process associated with numerous genetic alterations [2]. Accordingly, the elucidation of the molecular mechanisms in BC has been the subject of extensive research over past decades. Clinically, delayed diagnosis, recurrence, and metastasis are still the biggest obstacles to the treatment of BC [3]. Therefore, searching for the ideal biomarkers and novel therapeutic targets of BC are essential for the diagnosis and treatment of BC.

Immune system functions as a host defensive mechanism protecting against invading pathogens and transformed cells, including cancer [4]. It has long been recognized that the immune system plays dual roles in the development of tumors [5]. Many experimental in vitro and in vivo studies have demonstrated that the immune network plays a significant role in the development and progression of BC [6], [7]. However, the underlying mechanisms are still poorly understood, especially the mechanisms explaining how the immune system dysfunction in breast cancer development.

Long non-coding RNA (lncRNA) are functional RNAs longer than 200 nucleotides in length. Over past few decade advances in genome-wide analyses have revealed that the human genome encodes over 10,000 lncRNAs with little coding capacity [8]. For a long time these lncRNAs have been considered as transcriptional noises, however, growing evidence suggests that lncRNAs are key regulators which governing various biological processes such as genomic imprinting, transcription activation and inhibition, chromatin modification and tissue development [9]. Dysregulation of lncRNAs is associated with many human diseases, including various types of cancers [10]. More recently, many lncRNAs have been shown to exert oncogenic or tumor suppressor properties in BC [11]. The well-studied lncRNA HOTAIR, for example, was found to be overexpressed in breast tumors, and the expression of HOTAIR in primary breast tumors was characterized as a negative prognostic factor in BC patients [12]. Although a few lncRNAs’ information accumulated in cancer, the functions of majority of lncRNAs remain largely unknown.

Hence, the aim of the present study was to perform lncRNA expression profiling to identify lncRNAs that might help to better diagnose and treat breast cancer. We identified a set of lncRNAs that were differentially expressed in breast cancer. Moreover, this study indicated that the dysregulated lncRNAs may disturb the immune network and promote the development of breast cancer. These findings will aid in our understanding of lncRNA function in immune system and may provide a basis for the diagnosis and therapy of breast cancer.

Section snippets

Tissues collection

Samples of breast cancer tissues consisting of tumors and adjacent sections from patients who had invasive breast cancer were collected consecutively between January 2013 and March 2014 at Nanjing Maternity and Child Health Care Hospital, Nanjing, China. This study was approved by the ethical review committee of Nanjing Maternity and Child Health Care Hospital affiliated to Nanjing Medical University. None of these patients accepts radiotherapy or chemotherapy prior to the breast tumor

Profile of microarray data

ArrayStar, Inc. (Rockville, MD, USA) Human lncRNA Microarray V 3.0 is designed for the global profiling of human lncRNAs and protein-coding transcripts. According microarray expression profiling data, 33664 lncRNAs and 23516 mRNAs were detected. In addition, 1486 lncRNAs (log fold-change > 2.3) were found differently expressed between BC samples and its paired adjacent tissue samples. All these lncRNAs were obtained from authoritative databases, RefSeq, UCSC Knowngenes, Ensembl and many related

Discussions

Breast cancer is the most common form of cancer in women and the second leading cause of death in females after lung cancer [20]. The development of breast cancer is a complex multistep process associated with numerous genetic genes, tumor suppressor genes, oncogenes and tumor cells hematogeneous dissemination [21]. Accordingly, the elucidation of the molecular mechanisms in breast cancer has been the subject of extensive research over the past decades. Several large-scale analyses have

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Acknowledgments

We thank Miss Xun Lu (Jinling High School, Nanjing, China) for her help in collecting patient information. This work was supported by a Grant from the National Natural Science Foundation of China (No. 81172501)

References (28)

  • A. Khodadadi et al.

    IL-23/IL-27 ratio in peripheral blood of patients with breast cancer

    Iran J Med Sci

    (2014)
  • Z. Du et al.

    Integrative genomic analyses reveal clinically relevant long non-coding RNAs in human cancer

    Nat Struct Mol Biol

    (2013)
  • S.W. Cheetham et al.

    Long non-coding RNAs and the genetics of cancer

    Br J Cancer

    (2013)
  • H. Zhang et al.

    Long non-coding RNA: a new player in cancer

    J Hematol Oncol

    (2013)
  • Cited by (0)

    View full text