NEAT1 contributes to breast cancer progression through modulating miR‐448 and ZEB1

Abstract

Breast cancer is a kind of common female cancers. Increasing evidence has exhibited that lncRNAs exert a crucial role in breast cancer. So far, the mechanism of lncRNAs in breast cancer is still not well established. In our current study, we focused on the biological role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in breast cancer. We observed that NEAT1 levels were significantly increased in human breast cancer cells including MCF-7, MDA-MB-453, MDA-MB-231, and SKBR3 cells compared to normal mammary epithelial cells MCF-10A while miR-448 was decreased. We found that downregulation of NEAT1 was able to inhibit the growth of breast cancer cells and miR-448 mimic exerted the similar function. Bioinformatics analysis and dual luciferase reporter assays confirmed the negative correlation between NEAT1 and miR-448 in vitro. In addition, ZEB1 was predicted as a novel mRNA target of miR-448. Overexpression of NEAT1 can induce breast cancer cell growth, migration, and invasion by inhibiting miR-448 and upregulating ZEB1. It was demonstrated that NEAT1 can increase ZEB1 levels while miR-448 mimic can repress ZEB1. It was speculated in our study that NEAT1 can serve as a competing endogenous lncRNA (ceRNA) to modulate ZEB1 by sponging miR-448 in breast cancer. To conclude, we uncovered that NEAT1 participated in breast cancer progression by regulating miR-448 and ZEB1. NEAT1 can be provided as a vital biomarker in breast cancer diagnosis and treatment therapy.

LncRNA NEAT1 exacerbates non-small cell lung cancer by upregulating EIF4G2 via miR-582-5p sponging

“…Knockdown experiments revealed that NEAT1 accelerated the proliferation, metastasis and glycolysis, while restricting apoptosis of NSCLC cells. The protumor role of NEAT1 is in agreement with published articles, thus, NEAT1 facilitates the development of breast cancer via miR-448 and zinc finger E-box-binding homeobox 1 protein (ZEB1) [30], and NEAT1 contributes to the progression of colorectal cancer via the enzyme probable ATP-dependent RNA helicase DDX5 also known as DEAD box protein 5 or RNA helicase p68 (DDX5) [31]. LncRNAs regulate cellular physiological and pathological processes mainly by functioning as miRNAs sponges [32].…”

Downregulation of long non‐coding RNA Opa interacting protein 5‐antisense RNA 1 inhibits breast cancer progression by targeting sex‐determining region Y‐box 2 by microRNA‐129‐5p upregulation

“…lncRNAs have a mRNA‐like structure and can function as a ceRNA to competitively bind miRNAs to regulate the expression of mRNAs. For example, the lncRNA nuclear enriched abundant transcript 1 (NEAT1) is significantly increased in breast cancer cells and promotes the progression of breast cancer; NEAT1 was also found to function as a ceRNA to regulate ZEB1 through miR‐448 . The lncRNA small ubiquitin‐like modifier 1 pseudogene 3 (SUMO1P3) is highly expressed in breast cancer tissue samples and is associated with higher staging and worse prognosis .…”

“…For example, the lncRNA nuclear enriched abundant transcript 1 (NEAT1) is significantly increased in breast cancer cells and promotes the progression of breast cancer; NEAT1 was also found to function as a ceRNA to regulate ZEB1 through miR-448. 26 The lncRNA small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) is highly expressed in breast cancer tissue samples and is associated with higher staging and worse prognosis. 27 The long intergenic non-coding RNA regulator of reprogramming (ROR) is a ceRNA of miR-145 and regulates the expression of ARF6 in triple-negative breast cancer, thus regulating invasion.…”

Long noncoding RNA TP53TG1 promotes pancreatic ductal adenocarcinoma development by acting as a molecular sponge of microRNA‐96

“…Similarly, lncRNA HOTAIR may function as a ceRNA to regulate HER2 expression through competition for miR‐331‐3p, thus playing an oncogenic role in gastric pathogenesis . Other studies also showed that ceRNAs were involved in the tumorigenesis of multiple cancer types, including prostate, breast, liver and lung cancers and so on . Although ceRNA research is still in its initial stages, exploration of ceRNA interplay in cancer will provide new insight into mechanisms underlying the pathogenesis of cancers.…”