scholarly journals Noncoding RNAs Serve as Diagnosis and Prognosis Biomarkers for Hepatocellular Carcinoma

2019 ◽  
Vol 65 (7) ◽  
pp. 905-915 ◽  
Author(s):  
Chang Tan ◽  
Jingyi Cao ◽  
Lu Chen ◽  
Xiaochen Xi ◽  
Siqi Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Clinical Performance ◽  
Survival Rates ◽  
Noncoding Rnas ◽  
Area Under The Curve ◽  
Small Rna Sequencing ◽  
Diagnosis And Prognosis ◽  
Noninvasive Biomarkers

Abstract BACKGROUND Reliable noninvasive biomarkers for hepatocellular carcinoma (HCC) diagnosis and prognosis are urgently needed. We explored the potential of not only microRNAs (miRNAs) but other types of noncoding RNAs (ncRNAs) as HCC biomarkers. METHODS Peripheral blood samples were collected from 77 individuals; among them, 57 plasma cell-free RNA transcriptomes and 20 exosomal RNA transcriptomes were profiled. Significantly upregulated ncRNAs and published potential HCC biomarkers were validated with reverse transcription (RT)-qPCR in an independent validation cohort (60–150 samples). We particularly investigated the diagnosis and prognosis performance and biological function for 1 ncRNA biomarker, RN7SL1, and its S fragment. RESULTS We identified certain circulating ncRNAs escaping from RNase degradation, possibly through binding with RNA-binding proteins: 899 ncRNAs were highly upregulated in HCC patients. Among them, 337 genes were fragmented long noncoding RNAs, 252 genes were small nucleolar RNAs, and 134 genes were piwi-interacting RNAs. Forty-eight candidates were selected and validated with RT-qPCR, of which, 16 ncRNAs were verified to be significantly upregulated in HCC, including RN7SL1, SNHG1, ZFAS1, and LINC01359. Particularly, the abundance of RN7SL1 S fragment discriminated HCC samples from negative controls (area under the curve, 0.87; 95% CI, 0.817–0.920). HCC patients with higher concentrations of RN7SL1 S fragment had lower survival rates. Furthermore, RN7SL1 S fragment alone promoted cancer cell proliferation and clonogenic growth. CONCLUSIONS Our results show that various ncRNA species, not only miRNAs, identified in the small RNA sequencing of plasma are also able to serve as noninvasive biomarkers. Particularly, we identified a domain of srpRNA RN7SL1 with reliable clinical performance for HCC diagnosis and prognosis.

scholarly journals Development and Validation an Epigenetic Modification-related Signals for Diagnosis and Prognosis of Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Diguang Wen ◽  
Sheng Qiu ◽  
Zuojin Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Rna Binding ◽  
Cox Regression ◽  
Rna Binding Proteins ◽  
Epigenetic Modification ◽  
Lasso Regression ◽  
Cancer Dataset ◽  
Gene Signatures ◽  
Diagnosis And Prognosis

Abstract Background: Increasing evidence has indicated that abnormal epigenetic modification such as RNAm6a modification, histone modification, DNA methylation modification, RNA binding proteins and transcription factors, is correlated with Hepatocarcinogenesis. However, it is unknown how epigenetic modification associated genes contribute to the occurrence and clinical outcome of hepatocellular carcinoma (HCC). Thus, we constructed epigenetic modification associated model that may enhance the diagnosis and prognosis of HCC.METHODS: In this study, we focused on the clinical values of epigenetic modification associated genes for HCC. Our gene expression data were collected from TCGA and a HCC datasets from GEO dataset in order to ensure the reliability of data. Their function was analyzed by bioinformatics methods. We used lasso regression, SUV, logistic regression and cox regression to construct the diagnosis and prognosis models. We also constructed a nomogram for the practicability of the above-mentioned prognosis model. The above results have been verified in an independent liver cancer dataset from ICGC database. Furthermore, we carried out pan cancer analysis to verify the specificity of the above model.RESULT: A large number of epigenetic modification associated genes were significantly different in HCC and normal liver tissues. The gene signatures showed good performance for predicting the occurrence and survival of HCC patients verified by DCA and ROC curve.CONCLUSION: Gene signatures based on epigenetic modification associated genes can be used to identify the occurrence and prognosis of liver cancer.

scholarly journals Identification of proteins and miRNAs that specifically bind an mRNA in vivo

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Kathrin Theil ◽  
Koshi Imami ◽  
Nikolaus Rajewsky
Keyword(s):  
Rna Binding ◽  
De Novo ◽  
Rna Binding Proteins ◽  
Noncoding Rnas ◽  
Shotgun Proteomics ◽  
Small Rna Sequencing ◽  
C Elegans ◽  
Specific Transcript ◽  
Proteomics Approach

Abstract Understanding regulation of an mRNA requires knowledge of its regulators. However, methods for reliable de-novo identification of proteins binding to a particular RNA are scarce and were thus far only successfully applied to abundant noncoding RNAs in cell culture. Here, we present vIPR, an RNA-protein crosslink, RNA pulldown, and shotgun proteomics approach to identify proteins bound to selected mRNAs in C. elegans. Applying vIPR to the germline-specific transcript gld-1 led to enrichment of known and novel interactors. By comparing enrichment upon gld-1 and lin-41 pulldown, we demonstrate that vIPR recovers both common and specific RNA-binding proteins, and we validate DAZ-1 as a specific gld-1 regulator. Finally, combining vIPR with small RNA sequencing, we recover known and biologically important transcript-specific miRNA interactions, and we identify miR-84 as a specific interactor of the gld-1 transcript. We envision that vIPR will provide a platform for investigating RNA in vivo regulation in diverse biological systems.

scholarly journals Roles of long noncoding RNAs in Hepatocellular Carcinoma

2016 ◽  
Vol 11 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Diyu Huang ◽  
Jie Fang ◽  
Gaojian Luo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Stability ◽  
Target Genes ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Malignant Tumors ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Aberrant Expression ◽  
Comprehensive Review

AbstractLong noncoding RNAs (lncRNAs) are nonprotein coding transcripts longer than 200 nucleotides. Aberrant expression of lncRNAs has been found to be associated with hepatocellular carcinoma, one of the most malignant tumors. In this paper, we give a systematic and comprehensive review of existing literature about the involvement of lncRNAs in hepatocellular carcinoma. To date, evidence suggests that a number of lncRNAs, including HEIH, H19, HOTAIR, MALAT1, and PVT1, may regulate the transcription of target genes by recruiting histone-modifying complexes. Under certain circumstances, lncRNAs form RNA-dsDNA triplexes. Certain lncRNAs, such as HULC, HOTAIR, H19, HOTTIP and PTENP1, exhibit their biological roles by associating with microRNAs (miRNAs). In addition, by complementary base pairing with mRNAs or forming complexes with RNA binding proteins (RBPs), lncRNA-ATB, MALAT1 and PCNA-AS1 may mediate mRNA stability and splicing. In conclusion, interactions with DNA, RNA and proteins appears to be involved in lncRNAs’ participation in tumorigenesis and developmental processes related to hepatocellular carcinoma.

PlncRNADB: A Repository of Plant lncRNAs and lncRNA-RBP Protein Interactions

2019 ◽  
Vol 14 (7) ◽  
pp. 621-627 ◽  
Author(s):  
Youhuang Bai ◽  
Xiaozhuan Dai ◽  
Tiantian Ye ◽  
Peijing Zhang ◽  
Xu Yan ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Populus Trichocarpa ◽  
Noncoding Rnas ◽  
Reference Database ◽  
Protein Coding ◽  
Arabidopsis Lyrata ◽  
User Friendly

Background: Long noncoding RNAs (lncRNAs) are endogenous noncoding RNAs, arbitrarily longer than 200 nucleotides, that play critical roles in diverse biological processes. LncRNAs exist in different genomes ranging from animals to plants. Objective: PlncRNADB is a searchable database of lncRNA sequences and annotation in plants. Methods: We built a pipeline for lncRNA prediction in plants, providing a convenient utility for users to quickly distinguish potential noncoding RNAs from protein-coding transcripts. Results: More than five thousand lncRNAs are collected from four plant species (Arabidopsis thaliana, Arabidopsis lyrata, Populus trichocarpa and Zea mays) in PlncRNADB. Moreover, our database provides the relationship between lncRNAs and various RNA-binding proteins (RBPs), which can be displayed through a user-friendly web interface. Conclusion: PlncRNADB can serve as a reference database to investigate the lncRNAs and their interaction with RNA-binding proteins in plants. The PlncRNADB is freely available at http://bis.zju.edu.cn/PlncRNADB/.

scholarly journals Long noncoding RNAs as tumorigenic factors and therapeutic targets for renal cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Haiyan Shen ◽  
Guomin Luo ◽  
Qingjuan Chen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Noncoding Rnas ◽  
Protein Translation ◽  
Long Noncoding Rnas ◽  
In Vivo Studies

AbstractApproximately 338,000 patients are diagnosed with kidney cancer worldwide each year, and renal cell carcinoma (RCC), which is derived from renal epithelium, accounts for more than ninety percent of the malignancy. Next generation RNA sequencing has enabled the identification of novel long noncoding RNAs (lncRNAs) in the past 10 years. Recent studies have provided extensive evidence that lncRNAs bind to chromatin modification proteins, transcription factors, RNA-binding proteins and microRNAs, and thereby modulate gene expression through regulating chromatin status, gene transcription, pre-mRNA splicing, mRNA decay and stability, protein translation and stability. In vitro and in vivo studies have demonstrated that over-expression of oncogenic lncRNAs and silencing of tumor suppressive lncRNAs are a common feature of human RCC, and that aberrant lncRNA expression is a marker for poor patient prognosis, and is essential for the initiation and progression of RCC. Because lncRNAs, compared with mRNAs, are expressed in a tissue-specific manner, aberrantly expressed lncRNAs can be better targeted for the treatment of RCC through screening small molecule compounds which block the interaction between lncRNAs and their binding proteins or microRNAs.

Translational remodeling by RNA ‐binding proteins and noncoding RNAs

2021 ◽  
Author(s):  
J. J. David Ho ◽  
Jeffrey H. S. Man ◽  
Jonathan H. Schatz ◽  
Philip A. Marsden
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Noncoding Rnas

scholarly journals Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

2021 ◽  
Vol 22 (14) ◽  
pp. 7477
Author(s):  
Rok Razpotnik ◽  
Petra Nassib ◽  
Tanja Kunej ◽  
Damjana Rozman ◽  
Tadeja Režen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Protein ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Bioinformatics Analyses ◽  
Published Evidence

Circular RNAs (circRNAs) are increasingly recognized as having a role in cancer development. Their expression is modified in numerous cancers, including hepatocellular carcinoma (HCC); however, little is known about the mechanisms of their regulation. The aim of this study was to identify regulators of circRNAome expression in HCC. Using publicly available datasets, we identified RNA binding proteins (RBPs) with enriched motifs around the splice sites of differentially expressed circRNAs in HCC. We confirmed the binding of some of the candidate RBPs using ChIP-seq and eCLIP datasets in the ENCODE database. Several of the identified RBPs were found to be differentially expressed in HCC and/or correlated with the overall survival of HCC patients. According to our bioinformatics analyses and published evidence, we propose that NONO, PCPB2, PCPB1, ESRP2, and HNRNPK are candidate regulators of circRNA expression in HCC. We confirmed that the knocking down the epithelial splicing regulatory protein 2 (ESRP2), known to be involved in the maintenance of the adult liver phenotype, significantly changed the expression of candidate circRNAs in a model HCC cell line. By understanding the systemic changes in transcriptome splicing, we can identify new proteins involved in the molecular pathways leading to HCC development and progression.

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