The lncRNA NEAT1 facilitates cell growth and invasion via the miR-211/HMGA2 axis in breast cancer

doi:10.1016/j.ijbiomac.2017.07.053

International Journal of Biological Macromolecules

Volume 105, Part 1, December 2017, Pages 346-353

https://doi.org/10.1016/j.ijbiomac.2017.07.053 Get rights and content

Abstract

Long non-coding RNAs play a significant role in cancer metastasis. Studies have demonstrated that LncRNA NEAT1 promotes cancer progression. We aimed to explore whether NEAT1 regulated growth and invasion in breast cancer cells. We provided evidence that lncRNA NEAT1 was up-regulated in breast cancer cell lines and tissues. NEAT1 promoted invasion through inducing Epithelial-mesenchymal transition (EMT) and NEAT1 played a role in 5-fluorouracil (5-FU) resistance. In addition, we revealed a reciprocal repression between NEAT1 and miR-211. Furthermore, the EMT-inducer HMGA2 was identified as a down-stream target of miR-211. LncRNA NEAT1 induced EMT and 5-FU resistance through the miR-211/HMGA2 axis. Our findings suggest that lncRNA NEAT1 could be a new diagnostic biomarker and therapy target for breast cancer.

Introduction

Breast cancer, with an incidence of 370,000 deaths annually, is a common malignancy around the world. Invasion and metastasis significantly promote an aggressive breast cancer phenotype. Several studies have suggested that epithelial-mesenchymal transition (EMT) is a critical mechanism that contributes to the invasion and metastasis of breast cancer [1]. In addition, EMT often contributes to chemoresistance in breast cancer [2]. Thus, the identification of key inducers of EMT is of critical importance.

MicroRNAs (miRNAs) are small non-coding RNAs of about 22 nucleotides in length that are found in all eukaryotic cells. To date, studies have demonstrated that miRNAs play key roles in many biological processes, including tumorigenesis [3]. Recently, researchers found that miRNAs may potentially interact with long non-coding RNA (lncRNA) [4], [5].

LncRNAs are non-coding RNAs longer than 200 nt in length that play a significant role in various biological processes. Recently, researchers found that lncRNAs have a critical role in the progression of cancer [6], [7]. Interestingly, lncRNAs and miRNAs can interact with each other, imposing an additional level of posttranscriptional regulation [8], [9]. LncRNA NEAT1 is found to function as an oncogene in a series of cancers. Overexpression of lncRNA NEAT1 often contributes to cancer progression [10]. However, the role of lncRNA NEAT1 in breast cancer and its underlying mechanism is still poorly understood.

In the present study, we explored the role of lncRNA NEAT1 in promoting EMT as well as its interaction with miR-211 in breast cancer.

Section snippets

Cell culture and breast cancer tissue samples

The normal immortalized MCF-10A cells and the breast cancer cell lines MCF-7, MDA-MB-231, T-47-D and ZR-75-1were cultured in RPMI-1640 supplemented with 10% fetal bovine serum (FBS). All cells were maintained at 37 °C in a humidified atmosphere with 5% CO₂. Cell line MDA-MB-231 was used for all experiments described in this manuscript.

Tissue samples were obtained from breast cancer patients that were diagnosed by histo-pathology in the Guangdong General Hospital. This study was conducted with

NEAT1 was up-regulated in breast cancer cell lines and tissues

We detected the expression of NEAT1 in 118 human breast cancer tissues and adjacent normal breast tissues with the use of RT-PCR. It was found that the expression level of NEAT1 was significantly elevated in breast cancer tissues when compared with adjacent normal breast tissues (Fig. 1A). In addition, we found that NEAT1 expression was overexpressed in breast cancer cell lines when compared with normal immortalized MCF-10A cells (Fig. 1B).

NEAT1 expression was associated with poor prognosis and an aggressive breast cancer phenotype

We next explored the relation between NEAT1 expression

Dissussion

LncRNA NEAT1, which is transcribed from the familial tumor syndrome multiple endocrine neoplasia type 1 locus, comprises two isoforms (NEAT1_1 and NEAT1_2). Up-regulation of Neat1 may be a general feature of differentiation. For instance, Neat1 is up-regulated upon muscle differentiation and in-vitro neuronal differentiation. Recently, researchers have found that NEAT1 functions as an oncogene in a series of cancers. In bladder cancer, lncRNA NEAT1 promotes cell proliferation and migration [16]

Competing interests

The authors declare that they have no competing interest.

Authors’ contributions

Xuerui Li and Shuxia Wang designed the study. Zhenzhong Li, Xiaoyu Long and Zibai Guo contributed to the experimental procedures. Guochun Zhang and Jian Zu analyzed the data. Yu Chen and Linzhu Wen supervised all the work. All the authors have read and approved the final manuscript.

Acknowledement

This work was supported by a grant from Guangdong Science and Technology Department (No.S2013010014851).

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The lncRNA NEAT1 facilitates cell growth and invasion via the miR-211/HMGA2 axis in breast cancer

Abstract

Introduction

Section snippets

Cell culture and breast cancer tissue samples

NEAT1 was up-regulated in breast cancer cell lines and tissues

NEAT1 expression was associated with poor prognosis and an aggressive breast cancer phenotype

Dissussion

Competing interests

Authors’ contributions

Acknowledement

J. Biol. Chem.

Mol. Cell

Mol. Cell

J. Exp. Clin. Cancer Res.: CR

Mol. Cancer

Biochem. Biophys. Res. Commun.

Epithelial-mesenchymal Transition---A Hallmark of Breast Cancer Metastasis

Cancer hallmarks.

Nature

Cancer Res.

PLoS One

Cell. Death. Dis.

Cell Death Differ.

BMC Med. Genom.

Oncotarget

Nat. Cell Biol.