Dataset Information

Long Noncoding RNA Small Nucleolar Host Gene: A Potential Therapeutic Target in Urological Cancers.

ABSTRACT: The incidence of urological cancer has been gradually increasing in the last few decades. However, current diagnostic tools and treatment strategies continue to have limitations. Substantial evidence shows that long noncoding RNAs (lncRNAs) play essential roles in carcinogenesis and the progression, treatment response and prognosis of multiple human cancers, including urological cancers, gastrointestinal tumours, reproductive cancers and respiratory neoplasms. LncRNA small nucleolar RNA host genes (SNHGs), a subgroup of lncRNAs, have been found to be dysregulated in tumour cell biology. In this review, we summarize the impacts of lncRNA SNHGs in urological malignancies and the underlying mechanisms.

SUBMITTER: Yang Z

PROVIDER: S-EPMC8100577 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Long Noncoding RNA Small Nucleolar Host Gene: A Potential Therapeutic Target in Urological Cancers.

Yang Zitong Z Li Qinchen Q Zheng Xiangyi X Xie Liping L

Frontiers in oncology 20210422

The incidence of urological cancer has been gradually increasing in the last few decades. However, current diagnostic tools and treatment strategies continue to have limitations. Substantial evidence shows that long noncoding RNAs (lncRNAs) play essential roles in carcinogenesis and the progression, treatment response and prognosis of multiple human cancers, including urological cancers, gastrointestinal tumours, reproductive cancers and respiratory neoplasms. LncRNA small nucleolar RNA host gen ...[more]

PMID: 33968736

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Project description:BackgroundIncreasing evidence supports the role of small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) as master gene regulators at the epigenetic modification level. However, the underlying mechanism of these functional ncRNAs in colorectal cancer (CRC) has not been well investigated.MethodsThe dysregulated expression profiling of lncRNAs-snoRNAs-mRNAs and their correlations and co-expression enrichment were assessed by GeneChip microarray analysis. The candidate lncRNAs, snoRNAs, and target genes were detected by in situ hybridization (ISH), RT-PCR, qPCR and immunofluorescence (IF) assays. The biological functions of these factors were investigated using in vitro and in vivo studies that included CCK8, trans-well, cell apoptosis, IF assay, western blot method, and the xenograft mice models. rRNA 2'-O-methylation (Me) activities were determined by the RTL-P assay and a novel double-stranded primer based on the single-stranded toehold (DPBST) assay. The underlying molecular mechanisms were explored by bioinformatics and RNA stability, RNA fluorescence ISH, RNA pull-down and translation inhibition assays.ResultsTo demonstrate the involvement of lncRNA and snoRNAs in 2'-O-Me modification during tumorigenesis, we uncovered a previously unreported mechanism linking the snoRNPs NOP58 regulated by ZFAS1 in control of SNORD12C, SNORD78 mediated rRNA 2'-O-Me activities in CRC initiation and development. Specifically, ZFAS1 exerts its oncogenic functions and significantly up-regulated accompanied by elevated NOP58, SNORD12C/78 expression in CRC cells and tissues. ZFAS1 knockdown suppressed CRC cell proliferation, migration, and increased cell apoptosis, and this inhibitory effect could be reversed by NOP58 overexpression in vitro and in vivo. Mechanistically, the NOP58 protein could be recognized by the specific motif (AAGA or CAGA) of ZFAS1. This event accelerates the assembly of SNORD12C/78 to allow for further guiding of 2'-O-Me at the corresponding Gm3878 and Gm4593 sites. Importantly, silencing SNORD12C or 78 reduced the rRNAs 2'-O-Me activities, which could be rescued by overexpression ZFAS1, and this subsequently inhibits the RNA stability and translation activity of their downstream targets (e.g., EIF4A3 and LAMC2).ConclusionThe novel ZFAS1-NOP58-SNORD12C/78-EIF4A3/LAMC2 signaling axis that functions in CRC tumorigenesis provides a better understanding regarding the role of lncRNA-snoRNP-mediated rRNAs 2'-O-Me activities for the prevention and treatment of CRC.

Dataset Information

Long Noncoding RNA Small Nucleolar Host Gene: A Potential Therapeutic Target in Urological Cancers.

Publications

Long Noncoding RNA Small Nucleolar Host Gene: A Potential Therapeutic Target in Urological Cancers.

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