ZFAS1 promotes rRNA 2’O-methylationin by recruiting NOP58 contributes to colorectal cancer progression
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ABSTRACT:
PROVIDER: PRJNA565758 | ENA |
REPOSITORIES: ENA
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Project description:Increasing evidence suggested that small nucleolar RNAs (snoRNAs) and long non-coding RNAs (LncRNAs) were master regulators of gene regulation at epigenetic modification level, however, the underlying mechanism in colorectal cancer (CRC) have not been investigated. To demonstrate the involvement of LncRNA and snoRNAs in 2’-O-methylation (Me) in tumorigenesis, we develop the LncRNAs-snoRNAs microarray of paired CRC tissues, and found an unrecognized ZFAS1-NOP58- SNORD12C/78 signaling axis in CRC tumorigenesis through recognizing the consensus AAGA motif of ZFAS1 which directly binds to NOP58 protein, and accelerating the snoRNPs assemble for further guiding 2’-O-Me of 28S rRNA. Strikingly, overexpression SNORD12C/78 induces 2’-O-Me modification upon ZFAS1, and affects RNA stability and translation activity of their downstream targets (e.g., EIF4A3,LMAC2, etc.), thereby promoted CRC cell proliferation, invasion and inhibited apoptosis in vitro and in vivo. Thus, these results sheds new light on our understanding of lncRNAs-snoRNPs mediated rRNA 2'-O-methylations in CRC tumorigenesis.
2020-03-11 | GSE137511 | GEO
Project description:Increasing long non-coding RNAs (lncRNAs) have been reported to play key roles in the development and progression of various malignancies. ZNFX1 antisense RNA1 (ZFAS1) has been reported to be aberrant expression and suggested as a tumor suppressor or oncogene in many cancers. However, the biological role and underlying molecular mechanism of ZFAS1, especially the miRNA sponge role of which in CRC remain largely unknown. We found that ZFAS1 expression was higher in CRC tissues, where it was associated with poor overall survival (OS), we also showed that ZFAS1 upregulation was induced by nuclear transcription factor SP1. Moreover, ZFAS1 and VEGFA are both targets of miR-150-5p, while ZFAS1 binds to miR-150-5p in an AGO2-dependent manner. Additionally, ZFAS1 upregulation markedly promoted as well as ZFAS1 knockdown significantly suppressed CRC cell proliferation, migration, invasion and angiogenesis, and the inhibitory effect caused by ZFAS1 knockdown could be reversed by antagomiR-150-5p. Lastly, we demonstrated that ZFAS1 knockdown inhibited EMT process and inactivated VEGFA/VEGFR2 and downstream Akt/mTOR signaling pathway in CRC. Our data demonstrated that SP1-induced ZFAS1 contributed to CRC progression by upregulating VEGFA via competitively binding to miR-150-5p, which acts as a tumor suppressor by targeting VEGFA in CRC.
| S-EPMC6155123 | biostudies-literature
Project description:The aim of this study was to screen abnormal lncRNAs in the progression of hepatocellular carcinoma through high-throughput sequencing, and to screen the biomarkers for prognosis and diagnosis of hepatocellular carcinoma. Transcriptome analysis of 6 samples was completed in this project. A total of 93.581 Gb Clean Data (sequencing Data after quality control) was obtained. The average amount of Clean Data of each sample was 15.597 Gb. The Q30 base percentage was above 93.69 % and GC content was between 44.95% and 50.05%. In conclusion, sequencing analysis provided a landscape for abnormal regulation of lncRNAs, and screened out a significantly different lncRNAs ZFAS1. ZFAS1were found to be overexpressed in hepatocellular carcinoma tissues and correlated with malignant status and prognosis of hepatocellular carcinoma patients, and ZFAS1 silencing inhibited proliferation, migration and invasion of SK-Hep1 cells. The overexpression of miR-582-3p can eliminate the inhibitory effect of ZFAS1 silencing on SK-Hep1 cells, which may be valuable for the diagnosis and treatment of hepatocellular carcinoma. ZFAS1 may be a new potential biomarker for liver cancer. Further studies on the regulatory process of ZFAS1/miR-582-3p will help us to understand the mechanism of the occurrence and development of liver cancer
2021-10-16 | GSE185799 | GEO
Project description:The hereditary information encoded in DNA sequence is intrinsically susceptible to alterations, being continually threatened by a variety of genotoxic perturbations. To safeguard the stability of the genome, eukaryotic cells have evolved a set of sophisticated surveillance system that controls several aspects of the cellular response, including the detection of DNA lesions, a temporary cell cycle arrest, regulation of transcription, and the repair of the damaged DNA. However, it is still poorly understood how the DNA damage checkpoints and stalled RNAPII molecules convert a very limited amount of molecular-level information (even a single DNA lesion) in the context of an otherwise genome into regulation that halts and resumes the cell-cycle engine in a coordinated way. In this study, we reveal a map of extensive lncRNA transcription during DDR by using synchronized cells, leading to the unexpected identification of a poorly characterized mammalian lncRNA-ZFAS1. We describe that ZFAS1 functions as a key player of cellular response to DNA damage in both human and rodent cells by fine tuning RNAPII kinetics, suggesting a lncRNA-dependent transcriptional regulatory axis that maintains genomic stability upon DNA damage in mammalian cells.
2023-08-03 | GSE239615 | GEO
Project description:The hereditary information encoded in DNA sequence is intrinsically susceptible to alterations, being continually threatened by a variety of genotoxic perturbations. To safeguard the stability of the genome, eukaryotic cells have evolved a set of sophisticated surveillance system that controls several aspects of the cellular response, including the detection of DNA lesions, a temporary cell cycle arrest, regulation of transcription, and the repair of the damaged DNA. However, it is still poorly understood how the DNA damage checkpoints and stalled RNAPII molecules convert a very limited amount of molecular-level information (even a single DNA lesion) in the context of an otherwise genome into regulation that halts and resumes the cell-cycle engine in a coordinated way. In this study, we reveal a map of extensive lncRNA transcription during DDR by using synchronized cells, leading to the unexpected identification of a poorly characterized mammalian lncRNA-ZFAS1. We describe that ZFAS1 functions as a key player of cellular response to DNA damage in both human and rodent cells by fine tuning RNAPII kinetics, suggesting a lncRNA-dependent transcriptional regulatory axis that maintains genomic stability upon DNA damage in mammalian cells.
2023-08-03 | GSE239614 | GEO
Project description:Numerous long noncoding RNAs (lncRNAs) are generated in response to external stimuli, but the scope and functions of such activity are not known. Here, we provide insight into how the transcription of lncRNAs are connected to DNA damage response by identifying a lncRNA ZFAS1, which is required for cell cycle arrest, transcription regulation and DNA repair. Mechanistically, ZFAS1 facilitates the changing hyperphosphorylated forms of the large subunit of RNAPII around transcription initiation sites by directly targeting the regulated genes. We revealed extensive transcription shutdown and concomitant stimulated engagement of RNAPII-Ser2P are crucial for repair and cell survival upon genotoxic stress. Finally, ZFAS1 knockout in mice dampened transcription-coupled nucleotide excision repair (TC-NER) and led to kidney dysplasia. Our study extends the understanding of lncRNAs in DNA damage repair (DDR) and implies a protective role of lncRNA against DDR-deficient developmental disorders.
2024-06-02 | GSE268445 | GEO
Project description:Numerous long noncoding RNAs (lncRNAs) are generated in response to external stimuli, but the scope and functions of such activity are not known. Here, we provide insight into how the transcription of lncRNAs are connected to DNA damage response by identifying a lncRNA ZFAS1, which is required for cell cycle arrest, transcription regulation and DNA repair. Mechanistically, ZFAS1 facilitates the changing hyperphosphorylated forms of the large subunit of RNAPII around transcription initiation sites by directly targeting the regulated genes. We revealed extensive transcription shutdown and concomitant stimulated engagement of RNAPII-Ser2P are crucial for repair and cell survival upon genotoxic stress. Finally, ZFAS1 knockout in mice dampened transcription-coupled nucleotide excision repair (TC-NER) and led to kidney dysplasia. Our study extends the understanding of lncRNAs in DNA damage repair (DDR) and implies a protective role of lncRNA against DDR-deficient developmental disorders.
2024-06-02 | GSE268444 | GEO
Project description:Numerous long noncoding RNAs (lncRNAs) are generated in response to external stimuli, but the scope and functions of such activity are not known. Here, we provide insight into how the transcription of lncRNAs are connected to DNA damage response by identifying a lncRNA ZFAS1, which is required for cell cycle arrest, transcription regulation and DNA repair. Mechanistically, ZFAS1 facilitates the changing hyperphosphorylated forms of the large subunit of RNAPII around transcription initiation sites by directly targeting the regulated genes. We revealed extensive transcription shutdown and concomitant stimulated engagement of RNAPII-Ser2P are crucial for repair and cell survival upon genotoxic stress. Finally, ZFAS1 knockout in mice dampened transcription-coupled nucleotide excision repair (TC-NER) and led to kidney dysplasia. Our study extends the understanding of lncRNAs in DNA damage repair (DDR) and implies a protective role of lncRNA against DDR-deficient developmental disorders.
2024-06-02 | GSE268446 | GEO
Project description:Numerous long noncoding RNAs (lncRNAs) are generated in response to external stimuli, but the scope and functions of such activity are not known. Here, we provide insight into how the transcription of lncRNAs are connected to DNA damage response by identifying a lncRNA ZFAS1, which is required for cell cycle arrest, transcription regulation and DNA repair. Mechanistically, ZFAS1 facilitates the changing hyperphosphorylated forms of the large subunit of RNAPII around transcription initiation sites by directly targeting the regulated genes. We revealed extensive transcription shutdown and concomitant stimulated engagement of RNAPII-Ser2P are crucial for repair and cell survival upon genotoxic stress. Finally, ZFAS1 knockout in mice dampened transcription-coupled nucleotide excision repair (TC-NER) and led to kidney dysplasia. Our study extends the understanding of lncRNAs in DNA damage repair (DDR) and implies a protective role of lncRNA against DDR-deficient developmental disorders.
2024-06-02 | GSE268447 | GEO
Project description:lncRNA-ZFAS1, an emerging gate-keeper in DNA damage-dependent transcriptional regulation [ZFAS1 ChIRP-seq]
| PRJNA1000430 | ENA