Clinical significance and biological roles of small nucleolar RNAs in hepatocellular carcinoma (Review)

Baral, Dilip; Wu, Long; Katwal, Gaurav; Xiong, Yan; Wang, Yanfeng; Ye, Qifa

doi:10.3892/br.2018.1063

Cited by 14 publications

(12 citation statements)

References 41 publications

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“…In tissue, we observed a general downregulation of snoRNAs in tumor compared to normal. Studies have shown that snoRNAs are indeed downregulated in tumors [50] and in HCC [51]. In cancer serum vs control serum, snoRNAs were generally up-regulated and tRNAs were generally downregulated.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive transcriptomic analyses of tissue, serum, and serum exosomes from hepatocellular carcinoma patients

et al. 2019

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BackgroundThe expression of microRNAs (miRNAs) is a promising prognostic and diagnostic tool in hepatocellular carcinoma (HCC). Here we performed small RNA sequencing (sRNA-seq) of tissue, serum and serum exosomes to investigate changes in miRNA expression between the different sample types and correlated the expression with clinical parameters. We also performed gene expression arrays on tumor and normal tissue.ResultsPaired tissue, serum and serum exosomes sequencing revealed consistent positive correlation of miR-21 between serum exosomes and tumor tissue, indicating that miR-21 could be exported from tissue to circulation via exosomes. We found that let-7 miRNAs are generally upregulated in serum exosomes compared to whole serum, indicating that these miRNAs could be preferentially loaded into exosomes. Comparing serum from HCC patients with serum from healthy individuals revealed a global increase of miRNAs in serum from HCC patients, including an almost 4-fold increase of several miRNAs, including the liver-specific miR-122. When correlating miRNA expression with clinical parameters we detected significant association between hepatitis B virus (HBV) infection and miR-122 in serum as well as several serum and tissue-miRNAs that correlated with surgery type. We found that miR-141 and miR-146 correlated with cirrhosis in tumor tissue and normal tissue, respectively. Finally, high expression of miR-21 in tumors were associated with poor survival. Focusing on gene expression we found several significant messenger RNAs (mRNAs) between tumor and normal tissue and a Gene Ontology (GO) analysis revealed that these changes were mainly related to cell cycle and metabolism. Further, we detected mRNAs that correlated with cirrhosis and HBV infection in tissue. Finally, GO analysis of predicted targets for miRNAs down-regulated in tumor found that these were enriched for functions related to collagen synthesis.ConclusionsOur combined data point to altered miRNA and mRNA expression contributing to both generally impaired lipid metabolism and increased cell proliferation and a miRNA-driven increase in collagen synthesis in HCC. Our results further indicate a correlation in miRNA expression between exosomes, serum, and tissue samples suggesting export from tumors via exosomes. This correlation could provide a basis for a more tumor-specific miRNA profile in serum.

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Section: Discussionmentioning

confidence: 99%

Comprehensive transcriptomic analyses of tissue, serum, and serum exosomes from hepatocellular carcinoma patients

et al. 2019

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“…It has been reported that some of the snoRNAs and snoRNPs expression are coordinately upregulated in various types of cancers. For example, box H/ACA and DKC1 are upregulated in breast cancer, and box H/ACA, NOP10 and GAR1 are increased in HNSCC, suggesting that hyperactive snoRNP biogenesis is strongly required for the survival of cancer cells [23,[40], [41], [42]]. Given that the snoRNP complexes need R2TP for their assembly, R2TP expression could be coordinately upregulated in cancer cells.…”

Section: Oncogenesis-related Function Of R2tp/paqosomementioning

confidence: 99%

R2TP/PAQosome as a promising chemotherapeutic target in cancer

Kakihara

Kiguchi

Ohazama

et al. 2020

Japanese Dental Science Review

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R2TP/PAQosome (particle for arrangement of quaternary structure) is a novel multisubunit chaperone specialized in the assembly/maturation of protein complexes that are involved in essential cellular processes such as PIKKs (phosphatidylinositol 3-kinase-like kinases) signaling, snoRNP (small nucleolar ribonucleoprotein) biogenesis, and RNAP II (RNA polymerase II) complex formation. In this review article, we describe the current understanding of R2TP/PAQosome functions and characteristics as well as how the chaperone complex is involved in oncogenesis, highlighting DNA damage response, mTOR (mammalian target of rapamycin) pathway as well as snoRNP biogenesis. Also, we discuss its possible involvement in HNSCC (head and neck squamous cell carcinoma) including OSCC (oral squamous cell carcinoma). Finally, we provide an overview of current anti-cancer drug development efforts targeting R2TP/PAQosome.

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“…Among them, the lncRNA HULC has already been established as a diagnostic biomarker of HCC 36 . SnoRNAs also show clinical significance and play important roles in HCC 40 . Collectively, we selected five genes as potential exRNA biomarkers for further analysis and validation, including known biomarkers HULC and novel biomarker candidates LINC01226 , circ-0073052 , circ-0080695 , and SNORD3B-1 .…”

Section: Resultsmentioning

confidence: 99%

Integrative analysis of long extracellular RNAs reveals a detection panel of noncoding RNAs for liver cancer

Zhu

Wang

et al. 2021

Theranostics

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Rationale: Long extracellular RNAs (exRNAs) in plasma can be profiled by new sequencing technologies, even with low abundance. However, cancer-related exRNAs and their variations remain understudied. Methods: We investigated different variations (i.e. differential expression, alternative splicing, alternative polyadenylation, and differential editing) in diverse long exRNA species (e.g. long noncoding RNAs and circular RNAs) using 79 plasma exosomal RNA-seq (exoRNA-seq) datasets of multiple cancer types. We then integrated 53 exoRNA-seq datasets and 65 self-profiled cell-free RNA-seq (cfRNA-seq) datasets to identify recurrent variations in liver cancer patients. We further combined TCGA tissue RNA-seq datasets and validated biomarker candidates by RT-qPCR in an individual cohort of more than 100 plasma samples. Finally, we used machine learning models to identify a signature of 3 noncoding RNAs for the detection of liver cancer. Results: We found that different types of RNA variations identified from exoRNA-seq data were enriched in pathways related to tumorigenesis and metastasis, immune, and metabolism, suggesting that cancer signals can be detected from long exRNAs. Subsequently, we identified more than 100 recurrent variations in plasma from liver cancer patients by integrating exoRNA-seq and cfRNA-seq datasets. From these datasets, 5 significantly up-regulated long exRNAs were confirmed by TCGA data and validated by RT-qPCR in an independent cohort. When using machine learning models to combine two of these validated circular and structured RNAs ( SNORD3B-1, circ-0080695 ) with a miRNA ( miR-122 ) as a panel to classify liver cancer patients from healthy donors, the average AUROC of the cross-validation was 89.4%. The selected 3-RNA panel successfully detected 79.2% AFP-negative samples and 77.1% early-stage liver cancer samples in the testing and validation sets. Conclusions: Our study revealed that different types of RNA variations related to cancer can be detected in plasma and identified a 3-RNA detection panel for liver cancer, especially for AFP-negative and early-stage patients.

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Clinical significance and biological roles of small nucleolar RNAs in hepatocellular carcinoma (Review)

Cited by 14 publications

References 41 publications

Comprehensive transcriptomic analyses of tissue, serum, and serum exosomes from hepatocellular carcinoma patients

Comprehensive transcriptomic analyses of tissue, serum, and serum exosomes from hepatocellular carcinoma patients

R2TP/PAQosome as a promising chemotherapeutic target in cancer

Integrative analysis of long extracellular RNAs reveals a detection panel of noncoding RNAs for liver cancer

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