ZFAS1: a novel tumor-related long non-coding RNA

Dong, Dan; Mu, Zhongyi; Zhao, Chenghai; Sun, Mingli

doi:10.1186/s12935-018-0623-y

Cited by 70 publications

(65 citation statements)

References 57 publications

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“…[7][8][9] Zinc finger antisense 1 (ZFAS1), a member of lncRNAs, has been demonstrated to be a novel vital oncogenic ln-cRNA. 10,11 ZFAS1 is implicated in the occurrence and development of various cancers, including gastric cancer, ovarian cancer and hepatocellular carcinoma. 10 However, the role of ZFAS1 in glioma has not been fully understood.…”

Section: Introductionmentioning

confidence: 99%

ZFAS1 knockdown inhibits viability and enhances cisplatin cytotoxicity by up‐regulating miR‐432‐5p in glioma cells

Yang

Han

Feng

2019

Basic Clin Pharma Tox

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Background Long non‐coding RNA (lncRNA) zinc finger antisense 1 (ZFAS1) is a novel vital oncogenic lncRNA that is dysregulated in various types of cancers, including glioma. According to TargetScan prediction, miR‐432‐5p is a target of ZFAS1. Herein, we aimed to determine whether there was a correlation between ZFAS1 and miR‐432‐5p and to explore their roles in glioma. Methods The expression levels of ZFAS1 and microRNA (miR)‐432‐5p in clinical tissues and cell lines were measured using RT‐qPCR. Cell viability was detected using MTT assay. Cell apoptosis was examined using flow cytometry. The association between ZFAS1 and miR‐432‐5p was confirmed using luciferase reporter and RNA pull‐down assays. Results Zinc finger antisense 1 expression was up‐regulated, while miR‐432‐5p expression was down‐regulated in both glioma tissues and cells. Knockdown of ZFAS1 and miR‐432‐5p overexpression inhibited cell viability and enhanced the chemosensitivity of glioma cells to cisplatin. MiR‐432‐5p was a direct target of ZFAS1 in glioma cells. Inhibition of miR‐432‐5p blocked the effects of ZFAS1 knockdown on cell viability and cisplatin sensitivity. Conclusions Knockdown of ZFAS1 inhibited the viability and enhanced cisplatin sensitivity via targeting miR‐432‐5p in glioma cells.

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Section: Introductionmentioning

confidence: 99%

ZFAS1 knockdown inhibits viability and enhances cisplatin cytotoxicity by up‐regulating miR‐432‐5p in glioma cells

Yang

Han

Feng

2019

Basic Clin Pharma Tox

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“…6,13 Latest evidence on tumorigenesis has revealed that lncRNAs play a vital role in the tumorigenesis of many forms of cancers, 6,13 and several oncogenic lncRNAs, such as NEAT1, 7,14 MALAT1 15,16 and PVT1, 17 are well established. In addition, certain other lncRNAs, such as GAS5 18 and ZFAS1, 19 have been shown to act as tumour suppressors during carcinogenesis.…”

mentioning

confidence: 99%

Tumour suppressive long non‐coding RNA AFDN‐DT inhibits gastric cancer invasion via transcriptional regulation

Lai

Wang

et al. 2020

J Cellular Molecular Medi

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Emerging evidence has revealed that dysregulation of lncRNA is associated with the initiation and progression of cancer. However, the function of these lncRNAs in cancer remains largely unexplored. Here, we reported that AFDN‐DT, an lncRNA that is repressed in gastric cancers (GC), functions as a tumour suppressor by inhibiting cell growth and metastasis through transcriptional repression of genes involved in metastasis. Using in vitro and in vivo models, we demonstrated that overexpression of AFDN‐DT inhibited the proliferation and metastasis of GC. We found that AFDN‐DT was located at the nucleus and interacted with the chromatin in gastric cells. Further, ChIRP‐seq experiments and RNA‐seq analysis revealed that AFDN‐DT directly bound to the promoter regions and regulated the expression of genes essential for malignant transformation. Moreover, we demonstrated that DNA hypermethylation could repress AFDN‐DT expression and treatment with DNA methylation inhibitors restored its expression. Collectively, the results of our study demonstrated the tumour suppressive role of AFDN‐DT in GC and elucidated the transcription regulatory role of tumour suppressive lncRNAs, which can serve as potential prognostic markers for GC.

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“…There are variable results with the examination of ZFAS1 in the literature. 111 ZFAS1 has previously been shown to have a tumor suppressive function in breast cancer by decreasing both cell proliferation and migration. 141,142 Examination of ZFAS1 in hepatocellular carcinoma has shown that it can have both a tumor suppressive and oncogenic function through different mechanisms.…”

Section: Chapter XI Discussion and Concluding Remarksmentioning

confidence: 99%

“…There is therefore, a need to characterize the lncRNA expression profile for a specific cancer subtype. 111 Some investigators have shown that lncRNAs can have paradoxical effects in different cancers, which further underscores the reason for investigation in a particular cancer subtype. 111 The identification of differentially expressed lncRNA between colon adenocarcinoma and normal colon epithelium is important, as this may demonstrate lncRNAs that may be important in colon cancer carcinogenesis.…”

Section: Other Signaling Pathwaysmentioning

confidence: 99%

“…Additionally, ZFAS1 has recently been identified to have a complex role in tumor signaling in different cancers. 111 We propose that by manipulating ZFAS1 expression in our three colon cancer cell lines, that we will affect the expression of target miRNAs. These target miRNAs have been identified by using a bioinformatics predication tool, and have also been experimentally verified in the literature through positive luciferase reporter assays or RNA pulldown assays.…”

Section: Chapter IX Zfas1 Has a Reciprocal Relationship With Mir-200bmentioning

confidence: 99%

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The identification of long non-coding RNA ZFAS1 through an exploratory RNA-sequencing analysis and its association with epithelial-to-mesenchymal transition in colon cancer adenocarcinoma.

O’Brien¹

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Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to be significantly increased in expression in colon adenocarcinoma, three of viii which ZFAS1, GAS5, and PVT1 were found to be significantly increased in colon adenocarcinoma compared to paired normal colon epithelium as examined by laser capture microdissection. 2. Both ZFAS1 and GAS5 are significantly increased in cytoplasm of cell lines compared to the nucleus, whereas PVT1 was more represented in the nucleus. As such there was significant knockdown of both ZFAS1 and GAS5 following transfection with siRNA. 3. Knockdown of ZFAS1 leads to decreased proliferation and migration in colon adenocarcinoma cell lines. In contrast, knockdown of GAS5 did not lead to a change in proliferation. We focused our subsequent investigation on ZFAS1. 4. ZFAS1 has a reciprocal relationship with miR-200b and miR-200c expression in vitro but not with three of the other experimentally verified miRNAs that bind ZFAS1. We also validated the functional effect of miR-200b and miR-200c mimics on decreasing cell migration. 5. ZFAS1 knockdown is associated with the functional changes on cellular phenotype through decreasing ZEB1 expression through miR-200 signaling, causing a subsequent increase in the expression of the epithelial marker, E-cadherin, and a decrease in the expression of the mesenchymal marker, vimentin. These findings demonstrate an association between ZFAS1 and miR-200/ZEB1/Ecadherin, vimentin signaling in EMT signaling in colon adenocarcinoma. In contrast to typical EMT signaling, ZFAS1 knockdown also leads to decreased cell proliferation suggesting its potential value as a therapeutic agent.

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ZFAS1: a novel tumor-related long non-coding RNA

Cited by 70 publications

References 57 publications

ZFAS1 knockdown inhibits viability and enhances cisplatin cytotoxicity by up‐regulating miR‐432‐5p in glioma cells

ZFAS1 knockdown inhibits viability and enhances cisplatin cytotoxicity by up‐regulating miR‐432‐5p in glioma cells

Tumour suppressive long non‐coding RNA AFDN‐DT inhibits gastric cancer invasion via transcriptional regulation

The identification of long non-coding RNA ZFAS1 through an exploratory RNA-sequencing analysis and its association with epithelial-to-mesenchymal transition in colon cancer adenocarcinoma.

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