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Long noncoding RNA MEG3 inhibits breast cancer growth via upregulating endoplasmic reticulum stress and activating NF-κB and p53.

Abstract：

:Long noncoding RNA (lncRNA) maternally expressed 3 (MEG3) has been implicated as a tumor suppressor gene in several human cancer types. However, little is known regarding its involvement and potential mechanism in human breast cancer. In this study, we explored the effect of MEG3 on the growth of human breast cancer cell line MDA-MB-231 in vitro and in vivo, and sought to elucidate the potential signaling mechanisms. Ectopic overexpression of MEG3 using a lentiviral vector Lv-MEG3 significantly inhibited breast cancer cell growth in vitro and a cancer xenograft growth in vivo. MEG3 overexpression led to marked increase of apoptosis in breast cancer cells as determined using flow cytometry and fragmented DNA labeling. Moreover, ectopic expression of MEG3 increased the expression of endoplasmic reticulum (ER) stress-related proteins required for unfolded protein response, including glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1 (IRE1), protein kinase RNA (PKR)-like ER kinase (PERK), and activated transcription factor 6 (ATF6), as well as proapoptotic proteins CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-3. Finally, MEG3 overexpression markedly increased nuclear factor κB (NF-κB) expression, NF-κB translocation to the nucleus, and p53 expression, whereas pharmacological inhibition of NF-κB completely abolished MEG3-induced activation of p53. Together, these results suggest that MEG3 inhibits breast cancer growth and induces breast cancer apoptosis, partially via the activation of the ER stress, NF-κB and p53 pathways, and that NF-κB signaling is required for MEG3-induced p53 activation in breast cancer cells. Our results indicate targeting lncRNA MEG3 may represent a novel strategy for breast cancer therapy.

journal_name

J Cell Biochem

journal_title

Journal of cellular biochemistry

authors

Zhang Y,Wu J,Jing H,Huang G,Sun Z,Xu S

doi

10.1002/jcb.27982

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

6789-6797

issue

eissn

0730-2312

issn

1097-4644

journal_volume

120

pub_type

杂志文章

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Long noncoding RNA MEG3 inhibits breast cancer growth via upregulating endoplasmic reticulum stress and activating NF-κB and p53.