Long noncoding RNA ZEB1-AS1 epigenetically regulates the expressions of ZEB1 and downstream molecules in prostate cancer

Su, Wenjing; Xu, Miao; Chen, Xueqin; Chen, Ni; Gong, Jing; Nie, Ling; Li, Ling; Li, Xinglan; Zhang, Mengni; Zhou, Qiao

doi:10.1186/s12943-017-0711-y

Cited by 136 publications

(122 citation statements)

References 39 publications

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“…53,54 Notably, lncRNAs are frequently involved in regulatory processes of epigenetic modifications such as histone methylation and acetylation. 55 In the present study, the RIP assay and RNA pull-down demonstrated the binding of ZFAT-AS1 and EZH2. It has been reported that CDX2 is one of the developmental transcription factor families bound by SUZ12, and SUZ12 is bound to the CDX2 promoter region.…”

Section: Discussionsupporting

confidence: 53%

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

Zhang

Ruan

et al. 2020

Molecular Therapy

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Studies have found that RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) are dysregulated and play an important regulatory role in the development of tumors. Based on The Cancer Genome Atlas (TCGA) database, our findings from experiments, and the evidence of previous studies, we screened DiGeorge syndrome critical region gene 8 (DGCR8), ZFAT antisense RNA 1 (ZFAT-AS1), and caudal type homeobox 2 (CDX2) as research candidates. In the present study, DGCR8 and CDX2 were highly expressed and ZFAT-AS1 was markedly downregulated in glioma tissues and cells. DGCR8 or CDX2 knockdown or ZFAT-AS1 overexpression suppressed glioma cell proliferation, migration, and invasion and facilitated apoptosis. DGCR8 might decrease ZFAT-AS1 expression by attenuating its stability in a manner of inducing its cleavage. Importantly, ZFAT-AS1 could inhibit CDX2 transcription by mediating the methylation of histone H3 on lysine 27 (H3K27me3) modification induced by PRC2 in the CDX2 promoter region. In addition, CDX2 transcriptionally activated DGCR8 expression by binding to its promoter regions, forming a positive feedback loop of DGCR8/ZFAT-AS1/ CDX2. In conclusion, DGCR8/ZFAT-AS1 promotes CDX2 transcription in a PRC2 complex-dependent manner to facilitate the malignant biological behavior of glioma cells.

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Section: Discussionsupporting

confidence: 53%

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

Zhang

Ruan

et al. 2020

Molecular Therapy

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“…Previous studies have shown that the natural antisense transcripts play critical roles in various physiological and pathological processes through regulating gene promoter activation and transcription [30][31][32]. One such recognized is lncRNA ZEB1-AS1, which epigenetically activates ZEB1 and promotes prostate cancer metastasis [33]. Previously, lncRNA AFAP1-AS1 was reported to act as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis [34]; while Yin et al demonstrated that AFAP1-AS1 is associated with poor survival of patients with non-small cell lung cancer, and enhances cell proliferation via inhibition of p21 expression [35].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation

Han¹,

Gu²,

Lü³

et al. 2020

Mol Cancer

152

126

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Background: Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer.Methods: LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain-or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance.Results: AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level.Conclusion: Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.

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“…21,22 LncRNAs monitor carcinogenesis principally via modulating the expression levels of oncogenes or tumor suppressors. 19 Many studies revealed that LncRNA-ZEB2-AS1…”

Section: Discussionmentioning

confidence: 99%

“…The upstream antisense transcription may affect corresponding gene expression. 19 LncRNA-ZEB2-AS1 is an antisense lncRNA. We hypothesized that the antisense transcript lncRNA-ZEB2-AS1 modulates ZEB2 in breast cancer.…”

Section: Knockdown Of Lncrna-zeb2-as1 Led To the Down-regulation Ofmentioning

confidence: 99%

Long non‐coding RNA ZEB2‐AS1 promotes the proliferation, metastasis and epithelial mesenchymal transition in triple‐negative breast cancer by epigenetically activating ZEB2

Zhang

Liu

Sun

et al. 2019

J Cellular Molecular Medi

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The triple‐negative breast cancer is the most malignant type of breast cancer. Its pathogenesis and prognosis remain poor despite the significant advances in breast cancer diagnosis and therapy. Meanwhile, long noncoding RNAs (LncRNAs) play a pivotal role in the progression of malignant tumors. In this study, we found that LncRNA‐ZEB2‐AS1 was dramatically up‐regulated in our breast cancer specimens and cells (MDA231), especially in metastatic tumor specimens and highly invasive cells, and high lncRNA‐ZEB2‐AS1 expression is associated with clinicopathologic features and short survival of breast cancer patients. LncRNA‐ZEB2‐AS1 promotes the proliferation and metastasis of MDA231 cells in SCID mice. Thus, it is regarded as an oncogene in triple‐negative breast cancer. It is mainly endo‐nuclear and situated near ZEB2, positively regulating ZEB2 expression and activating the epithelial mesenchymal transition via the PI3K/Akt/GSK3β/Zeb2 signaling pathway. Meanwhile, EGF‐induced F‐actin polymerization in MDA231 cells can be suppressed by reducing lncRNA‐ZEB2‐AS1 expression. The migration and invasion of triple‐negative breast cancer can be altered through cytoskeleton rearrangement. In summary, we demonstrated that lncRNA‐ZEB2‐AS1 is an important factor affecting the development of triple‐negative breast cancer and thus a potential oncogene target.

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Long noncoding RNA ZEB1-AS1 epigenetically regulates the expressions of ZEB1 and downstream molecules in prostate cancer

Cited by 136 publications

References 39 publications

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation

Long non‐coding RNA ZEB2‐AS1 promotes the proliferation, metastasis and epithelial mesenchymal transition in triple‐negative breast cancer by epigenetically activating ZEB2

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