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Prognostic role of long noncoding RNA ZFAS1 in cancer patients: a systematic review and meta-analysis.

ABSTRACT: Long noncoding RNA ZFAS1 has been identified as a crucial role in the tumorigenesis of malignant tumors. Numerous studies reported that the expression levels of ZFAS1 in tumor tissues were dramatically higher than that in adjacent normal tissues. We conducted a meta-analysis to investigate the correlation between ZFAS1 expression and clinical outcomes of cancer patients. The databases of PubMed, EMBASE, Web of Science, Cochrane Library, CNKI and WanFang were retrieved for eligible studies. A total of 841 patients from 9 studies were eventually included. Our results demonstrated that increased ZFAS1 expression was significantly associated with poor OS in cancer patients (HR = 2.13, 95% CI = 1.71-2.65, P < 0.001). Patients with high ZFAS1 expression presented shorter RFS than those with low ZFAS1 expression (HR = 2.00, 95% CI = 1.45-2.77, P < 0.001). The clinicopathological parameters analysis demonstrated that increased ZFAS1 expression was significantly associated with vascular invasion (OR = 2.26, 95% CI = 1.36-3.78, P = 0.002), lymph node metastasis (OR = 2.98, 95% CI = 2.12-4.19, P < 0.001) and advanced TNM stage (OR = 3.00, 95% CI = 2.18-4.12, P < 0.001). In conclusion, lncRNA ZFAS1 might serve as a prognostic biomarker for cancer patients and increased ZFAS1 expression may be closely related to advanced characteristics of cancer.

SUBMITTER: Lan T

PROVIDER: S-EPMC5725037 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Prognostic role of long noncoding RNA ZFAS1 in cancer patients: a systematic review and meta-analysis.

Lan Tian T Lan Xiong X Li Guangcai G Zheng Zhen Z Zhang Minghua M Qin Faxiang F

Oncotarget 20170711 59

Long noncoding RNA ZFAS1 has been identified as a crucial role in the tumorigenesis of malignant tumors. Numerous studies reported that the expression levels of ZFAS1 in tumor tissues were dramatically higher than that in adjacent normal tissues. We conducted a meta-analysis to investigate the correlation between ZFAS1 expression and clinical outcomes of cancer patients. The databases of PubMed, EMBASE, Web of Science, Cochrane Library, CNKI and WanFang were retrieved for eligible studies. A tot ...[more]

PMID: 29245995

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Project description:BackgroundMost of the eukaryotic genome is transcribed, yielding a complex network of transcripts including thousands of lncRNAs that generally lack protein coding potential. However, only a small percentage of these molecules has been functionally characterised, and discoveries of specific functions demonstrate layers of complexity. A large percentage of lncRNAs is located in the cytoplasm, associated with ribosomes but the function of the majority of these transcripts is unclear. The current study analyses putative mechanisms of action of the lncRNA species member ZFAS1 that was initially discovered by microarray analysis of murine tissues undergoing mammary gland development. As developmental genes are often deregulated in cancer, here we have studied its function in breast cancer cell lines.ResultsUsing human breast cancer cell lines, ZFAS1 was found to be expressed in all cell lines tested, albeit at different levels of abundance. Following subcellular fractionation, human ZFAS1 was found in both nucleus and cytoplasm (as is the mouse orthologue) in an isoform-independent manner. Sucrose gradients based on velocity sedimentation were utilised to separate the different components of total cell lysate, and surprisingly ZFAS1 was primarily co-localised with light polysomes. Further investigation into ribosome association through subunit dissociation studies showed that ZFAS1 was predominantly associated with the 40S small ribosomal subunit. The expression levels of ZFAS1 and of mRNAs encoding several ribosomal proteins that have roles in ribosome assembly, production and maturation were tightly correlated. ZFAS1 knockdown significantly reduced RPS6 phosphorylation.ConclusionA large number of lncRNAs associate with ribosomes but the function of the majority of these lncRNAs has not been elucidated. The association of the lncRNA ZFAS1 with a subpopulation of ribosomes and the correlation with expression of mRNAs for ribosomal proteins suggest a ribosome-interacting mechanism pertaining to their assembly or biosynthetic activity. ZFAS1 may represent a new class of lncRNAs which associates with ribosomes to regulate their function.ReviewersThis article was reviewed by Christine Vande Velde, Nicola Aceto and Haruhiko Siomi.

Project description:BackgroundThe aberrant regulation of MALAT1 has been indicated to be involved in various carcinogenic pathways contributing to the tumourigenesis and progression of cancers. The current meta-analysis summarized the research advances of MALAT1 functions and analyzed its prognostic value among multiple types of cancers.MethodsEligible studies were identified through retrieving the PubMed, Web of Science, and CNKI databases, up to Mar 1, 2018. 28 studies of 5436 patients and 36 studies of 3325 patients were enrolled in the meta-analysis to evaluate the association of MALAT1 expression with survival outcomes and clinical parameters.ResultsThe results demonstrated that over-expression of MALAT1 may predict lymph node metastasis (pooled OR = 2.335, 95% CI 1.606-3.395, P = 0.000) and distant metastasis (pooled OR = 2.456, 95% CI 1.407-4.286, P = 0.002). Moreover, MALAT1 was also related with tumour size (pooled OR = 1.875, 95% CI 1.257-2.795, P = 0.002) and TNM stage (pooled OR = 2.034, 95% CI 1.111-3.724, P = 0.021). Additionally, elevated MALAT1 expression could predict poor OS (pooled HR = 2.298, 95% CI 1.953-2.704, P = 0.000), DFS (pooled HR = 2.036, 95% CI 1.240-3.342, P = 0.005), RFS (pooled HR = 2.491, 95% CI 1.505-4.123, P = 0.000), DSS (pooled HR = 2.098, 95% CI 1.372-3.211, P = 0.001) and PFS (pooled HR = 1.842, 95% CI 1.138-2.983, P = 0.013) in multivariate model. Importantly, subgroup analyses disclosed that increased MALAT1 expression had a poor OS among different cancer types (Estrogen-dependent cancer: pooled HR = 2.656, 95% CI 1.560-4.523; urological cancer: pooled HR = 1.952, 95% CI 1.189-3.204; glioma: pooled HR = 2.315, 95% CI 1.643-3.263; digestive cancer: pooled HR = 2.451, 95% CI 1.862-3.227).ConclusionsThe present findings demonstrated that MALAT1 may be a novel biomarker for predicting survival outcome, lymph node metastasis and distant metastasis.

Project description:BACKGROUND:Increasing 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. METHODS:The 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. RESULTS:To 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). CONCLUSION:The 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

Prognostic role of long noncoding RNA ZFAS1 in cancer patients: a systematic review and meta-analysis.

Publications

Prognostic role of long noncoding RNA ZFAS1 in cancer patients: a systematic review and meta-analysis.

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