Zinc finger antisense 1: A long noncoding RNA with complex roles in human cancers

Jiang, Xiaodi; Yang, Zhi; Li, Zhiwei

doi:10.1016/j.gene.2018.11.075

Cited by 20 publications

(9 citation statements)

References 63 publications

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“…In our bioinformatics analysis of TCLA and TANRIC [29] data, two additional upregulated lncRNAs with significant prognostic value were identified; however, increased expression of these lncRNAs was associated favorable prognosis. Among them, ZFAS1 is dysregulated and acts as either an oncogene or a tumor suppressor in various human malignancies [40, 41]. In CRC, recent studies have shown that ZFAS1 acts as an oncogene during tumorigenesis [42, 43].…”

Section: Discussionmentioning

confidence: 99%

LncRNA CASC9 interacts with CPSF3 to regulate TGF-β signaling in colorectal cancer

Luo

Geng

Zhang

et al. 2019

J Exp Clin Cancer Res

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Background Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related death worldwide. Increasing evidence indicates that the deregulation of long noncoding RNAs (lncRNAs) contributes to tumor initiation and progression; however, little is known about the biological role of cancer susceptibility candidate 9 (CASC9) in CRC. Methods Novel lncRNAs potentially involved in CRC tumorigenesis were identified from datasets downloaded from The Cancer LncRNome Atlas and The Atlas of Noncoding RNAs in Cancer. The CRC cell lines HCT-116, HCT-116 p53 −/− , SW620, SW480, HT-29, LoVo, LS-174T, and RKO were used. Colony-formation, MTS, cell-cycle, apoptosis, and in-vivo tumorigenesis assays were used to determine the role of CASC9 in CRC cell growth in vitro and in vivo. Potential interaction between CASC9 and cleavage and polyadenylation specificity factor subunit 3 (CPSF3) was evaluated using RNA immunoprecipitation and RNA-protein pull-down assays. RNA-sequencing was performed to analyze gene expression following CASC9 knockdown. RT-qPCR, western blotting, and mRNA decay assays were performed to study the mechanisms involved. Results CASC9 was frequently upregulated in CRC, which was correlated with advanced TNM stage, and higher CASC9 levels were associated with poor patient outcomes. Knockdown of CASC9 inhibited growth and promoted apoptosis in CRC cells, whereas ectopic CASC9 expression promoted cell growth in vitro and in vivo. We demonstrated that CPSF3 is a CASC9-interacting protein, and knockdown of CPSF3 mimicked the effects of CASC9 knockdown in CRC cells. Furthermore, we found that CASC9 exerts its oncogenic activity by modulating TGFβ2 mRNA stability and upregulating the levels of TGFβ2 and TERT, resulting in an increase in phosphorylated SMAD3 and activation of TGF-β signaling, and enhanced TERT complex function in CRC cells. Finally, CPSF3 was significantly upregulated in CRC tissues as compared with adjacent or non-adjacent normal colon tissues, and CASC9, CPSF3, and TGFβ2 levels in human CRC tissues were positively correlated. Conclusions CASC9 is a promising prognostic predictor for patients with CRC and the CASC9-CPSF3-TGFβ2 axis is a potential therapeutic target for CRC treatment. Electronic supplementary material The online version of this article (10.1186/s13046-019-1263-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

LncRNA CASC9 interacts with CPSF3 to regulate TGF-β signaling in colorectal cancer

Luo

Geng

Zhang

et al. 2019

J Exp Clin Cancer Res

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“…39,40 The expression of ZFAS1 is downregulated in breast cancer and acts as a tumor-suppressive gene; 41 in contrast, ZFAS1 is upregulated in colorectal, gastric, hepatocellular, bladder, and ovarian cancers, acting as an oncogene; and ZFAS1 is dysregulated in various malignant tumors and is involved in tumor proliferation, invasion, metastasis, apoptosis, cell cycle, and drug resistance. 42 Many proteins interact with the transcribed RNAs to form RNPs. RBPs, in the form of RNPs, modulate the fate of binding RNAs by regulating transcription, editing, splicing, polyadenylation, translocation, and turnover.…”

Section: Discussionmentioning

confidence: 99%

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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“…11 By interacting with diverse molecules, ZFAS1 regulates different processes including cell cycle, metastasis, invasion, proliferation and apoptosis. 12 LncRNAs have been widely studied to mediate chemoresistance. [13][14][15] In cervical cancer, silencing ZFAS1 inhibits cell migration, invasion and proliferation as well as enhances cisplatin chemosensitivity.…”

Section: Introductionmentioning

confidence: 99%

<p>ZFAS1 Promotes Cisplatin Resistance via Suppressing miR-421 Expression in Oral Squamous Cell Carcinoma</p>

Wang¹,

Hao²,

Wang³

et al. 2020

CMAR

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Oral squamous cell carcinoma (OSCC), with high incidence and mortality, represents one of the main reasons for head and neck malignant tumors. We want to investigate the effect of ZFAS1 on DDP resistance in oral squamous cell carcinoma. Methods: The proliferation and migration of cells was detected by CCK-8 and Transwell assay. The apoptosis was measured by flow cytometry and Western blot. The interaction of ZFAS1, miR-421, and MEIS2 was verified by luciferase reporter assay. The role of ZFAS1 in DDP resistance in vivo was tested by the nude mice model. The expression of ZFAS1 in exosomes from cisplatin-resistant patients was also determined. Results: ZFAS1 overexpression improved OSCC cell growth and inhibited OSCC cell susceptibility to DDP. In addition, the silencing of ZFAS1 promoted DDP-induced apoptosis. ZFAS1 directly bound to miR-421, which was verified by luciferase reporter assay. Inhibition of miR-421 reversed the effect of si-ZFAS1, which promoted the cell viability and decreased the sensitivity of DDP in DDP-resistant cells. The in vivo experiment showed the role of ZFAS1 in increasing the DDP resistance in OSCC tumor. Importantly, this study also showed upregulated ZFAS1 in serum exosomes derived from cisplatin-resistant patients. Conclusion: ZFAS1 promotes chemoresistance of oral squamous cell carcinoma to cisplatin and might become a latent therapeutic target for treating OSCC.

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Zinc finger antisense 1: A long noncoding RNA with complex roles in human cancers

Cited by 20 publications

References 63 publications

LncRNA CASC9 interacts with CPSF3 to regulate TGF-β signaling in colorectal cancer

LncRNA CASC9 interacts with CPSF3 to regulate TGF-β signaling in colorectal cancer

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

<p>ZFAS1 Promotes Cisplatin Resistance via Suppressing miR-421 Expression in Oral Squamous Cell Carcinoma</p>

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