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Long noncoding RNA RP4 functions as a competing endogenous RNA through miR-7-5p sponge activity in colorectal cancer

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World Journal of Gastroenterology 2018年第9期24卷 1004-1012页

作者： Mu-Lin Liu Qiao Zhang Xiao Yuan Long Jin Li-Li Wang Tao-Tao Fang Wen-Bin Wang Department of Gastrointestinal Surgery the First Affiliated Hospital of Bengbu Medical College Department of General Surgery the First Affiliated Hospital of Xinxiang Medical University Department of General Surgery the Fourth Affiliated Hospital of Anhui Medical University

AIM To investigate the role of long noncoding RNA(lnc RNA) RP4 in colorectal *** Lentivirus-mediated lnc RNA RP4 overexpression and knockdown were performed in the colorectal cancer cell line SW480. Cell proliferation, tumor growth, and early apoptosis were evaluated by a cell counting kit-8 assay, an in vivo xenograft tumor model, and annexin V/propidium iodide staining, respectively. Analysis of the lnc RNA RP4 mechanism involved assessment of the association of its expression with mi R-7-5 p and the SH3 GLB1 gene. Western blot analysis was also performed to assess the effect of lnc RNA RP4 on the autophagy-mediated cell death pathway and phosphatidylinositol-3-kinase(PI3 K)/Akt *** Cell proliferation, tumor growth, and early apoptosis in SW480 cells were negatively regulated by lnc RNA RP4. Functional experiments indicated that lnc RNA RP4 directly upregulated SH3 GLB1 expression by acting as a competing endogenous RNA(ce RNA) for mi R-7-5 p. This interaction led to activation of the autophagy-mediated cell death pathway and de-repression of PI3 K and Akt phosphorylation in colorectal cancer cells in *** Our results demonstrated that lnc RNA RP4 is a ce RNA that plays an important role in the pathogenesis of colorectal cancer, and could be a potential therapeutic target for colorectal cancer treatment.

关键词： Colorectal cancer long noncoding RNA RP4 SH3GLB1 miR-7-5p competing endogenous RNA

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Trans-natural antisense transcripts including noncoding RNAs in 10 species: implications for expression regulation

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NUCLEIC ACIDS RESEARCH 2008年第15期36卷 4833-4844页

作者： Li, Jiong-Tang Zhang, Yong Kong, Lei Liu, Qing-Rong Wei, Liping Peking Univ Ctr Bioinformat Natl Lab Prot Engn & Plant Genet Engn Coll Life Sci Beijing 100871 Peoples R China NIDA IRP DHHS Mol Neurobiol Branch NIH Baltimore MD 21224 USA

Natural antisense transcripts are at least partially complementary to their sense transcripts. Cis-Sense/Antisense pairs (cis-SAs) have been extensively characterized and known to play diverse regulatory roles, whereas trans-Sense/Antisense pairs (trans-SAs) in animals are poorly studied. We identified long trans-SAs in human and nine other animals, using ESTs to increase coverage significantly over previous studies. The percentage of transcriptional units (TUs) involved in trans-SAs among all TUs was as high as 4.13%. Particularly 2896 human TUs (or 2.89% of all human TUs) were involved in 3327 trans-SAs. Sequence complementarities over multiple segments with predicted RNA hybridization indicated that some trans-SAs might have sophisticated RNA-RNA pairing patterns. One-fourth of human trans-SAs involved noncoding TUs, suggesting that many noncoding RNAs may function by a trans-acting antisense mechanism. TUs in trans-SAs were statistically significantly enriched in nucleic acid binding, ion/protein binding and transport and signal transduction functions and pathways;a significant number of human trans-SAs showed concordant or reciprocal expression pattern;a significant number of human trans-SAs were conserved in mouse. This evidence suggests important regulatory functions of trans-SAs. In 30 cases, trans-SAs were related to cis-SAs through paralogues, suggesting a possible mechanism for the origin of trans-SAs. All trans-SAs are available at http://***/.

关键词： .RNAs noncoding pairing antisense transcripts Natural antisense cis-SAs human trans-SAs

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Long noncoding RNA HOXA11-AS promotes gastric cancer cell proliferation and invasion via SRSF1 and functions as a biomarker in gastric cancer

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World Journal of Gastroenterology 2019年第22期25卷 2763-2775页

作者： Yun Liu Yu-Mei Zhang Feng-Bo Ma Su-Rong Pan Bao-Zhen Liu Department of Operating Room Binzhou People's HospitalBinzhou 256610Shandong ProvinceChina Department of Return Visit Binzhou People's HospitalBinzhou 256610Shandong ProvinceChina Department of Gastroenterology Binzhou People's HospitalBinzhou 256610Shandong ProvinceChina

BACKGROUND Gastric cancer (GC) is the fourth most frequent malignancy all over the world. The diagnosis of GC is challenging and the prognosis of GC is very unfavorable. Accumulating evidence reveals that serum long noncoding RNAs (lncRNAs) can function as biomarkers in various types of cancers, including GC. AIM To explore the level and molecular mechanism of the lncRNA HOXA11-AS in GC and the diagnostic and prognostic significance of serum HOXA11-AS in GC. METHODS HOXA11-AS levels in GC tissue, cell lines, and serum samples were measured. The correlation between HOXA11-AS expression and clinicopathological characteristics was analyzed. The role of HOXA11-AS in the diagnosis and prognosis of GC was evaluated. Cell function assays were performed for exploration of the roles of HOXA11-AS in GC cells. Moreover, Western blot was performed to explore the target regulated by HOXA11-AS in GC cells. RESULTS Up-regulation of HOXA11-AS was found in GC tissues, cell lines, and serum samples. In GC patients, decreased serum HOXA11-AS levels were negatively related with tumor size, TNM stage, and lymph node metastasis. The area under the receiver operating characteristic curve of serum HOXA11-AS in the diagnosis of GC was 0.924 (95%CI: 0.881-0.967;sensitivity, 0.787;specificity 0.978). Results of the Kaplan-Meier survival curves suggested the GC patients with a lower HOXA11-AS level having a better overall survival rate. HOXA11-AS promoted GC cell proliferation and invasion. SRSF1 may be the target regulated by HOXA11-AS in GC cells. CONCLUSION HOXA11-AS promotes GC cell proliferation and invasion via SRSF1 and may function as a promising marker in GC.

关键词： Long noncoding RNA HOXA11-AS SRSF1 Gastric cancer Biomarker

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Senescence-associated lncRNAs: senescence-associated long noncoding RNAs

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AGING CELL 2013年第5期12卷 890-900页

作者： Abdelmohsen, Kotb Panda, Amaresh Kang, Min-Ju Xu, Jason Selimyan, Roza Yoon, Je-Hyun Martindale, Jennifer L. De, Supriyo Wood, William H., III Becker, Kevin G. Gorospe, Myriam NIA Genet Lab Intramural Res Program NIH Baltimore MD 21224 USA

noncoding RNAs include small transcripts, such as microRNAs and piwi-interacting RNAs, and a wide range of long noncoding RNAs (lncRNAs). Although many lncRNAs have been identified, only a small number of lncRNAs have been characterized functionally. Here, we sought to identify lncRNAs differentially expressed during replicative senescence. We compared lncRNAs expressed in proliferating, early-passage, 'young' human diploid WI-38 fibroblasts [population doubling (PDL) 20] with those expressed in senescent, late-passage, 'old' fibroblasts (PDL 52) by RNA sequencing (RNA-Seq). Numerous transcripts in all lncRNA groups (antisense lncRNAs, pseudogene-encoded lncRNAs, previously described lncRNAs and novel lncRNAs) were validated using reverse transcription (RT) and real-time, quantitative (q)PCR. Among the novel senescence-associated lncRNAs (SAL-RNAs) showing lower abundance in senescent cells, SAL-RNA1 (XLOC_023166) was found to delay senescence, because reducing SAL-RNA1 levels enhanced the appearance of phenotypic traits of senescence, including an enlarged morphology, positive beta-galactosidase activity, and heightened p53 levels. Our results reveal that the expression of known and novel lncRNAs changes with senescence and suggests that SAL-RNAs play direct regulatory roles in this important cellular process.

关键词： senescence-associated gene expression patterns proliferation post-transcriptional gene regulation noncoding transcriptome

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Inferences about human demography based on multilocus analyses of noncoding sequences

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GENETICS 2002年第3期161卷 1209-1218页

作者： Pluzhnikov, A Di Rienzo, A Hudson, RR Univ Chicago Dept Ecol & Evolut Chicago IL 60637 USA Univ Chicago Dept Human Genet Chicago IL 60637 USA

Data from 10 unlinked autosomal noncoding regions, resequenced in 15 individuals from each of three populations, were used in a multilocus analysis to test models of human demography. Each of the 10 regions consisted of similar to2500 bp. The multilocus analysis, based on summary statistics (average and variance of Tajima's D and Fu and Li's D*), was used to test a family of models with recent population expansion. The African sample (Hausa of Cameroon) is compatible with a constant population size model and a range of models with recent expansion. For this population sample, we estimated confidence sets that showed the limited range of parameter values compatible with growth. For an exponential growth rate as low as 1 X 10(-3)/generation, population growth is unlikely to have started prior to 50,000 years ago. For higher growth rates, the onset of growth must be more recent. On the basis of the average value of Tajima's D, our sample from an Italian population was found to be incompatible with a constant population size model or any simple expansion model. In the Chinese sample, the variance of Tajima's D was too large to be compatible with the constant population size model or any simple expansion model.

关键词： .population growth noncoding inferences compatible exponential Summary multilocus recent population constant population Hausa Human Demography size model

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Long noncoding RNA UCA1 Overexpression Is Associated with Poor Prognosis in Digestive System Malignancies: A Meta-analysis

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Current Medical Science 2019年第5期39卷 694-701页

作者： Fei-tao SHI Li-dong CHEN Lian-feng ZHANG Department of Gastroenterology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Long noncoding RNA(IncRNA)urothelial carcinoma associated 1(UCA1)has been reported to be highly expressed in many kinds of *** meta-analysis summarized its potential prognostic value in digestive system malignancies.A meta-analysis was performed through a comprehensive search in PubMed,EMBASE,the Cochrane Library,Web of Science and Chinese National Knowledge Infrastructure(CNKI)for suitable articles on the prognostic impact of UCA1 in digestive system malignancies from inception to June 27,*** hazard ratios(HRs)with 95% confidence interval(95%CI)were calculated to summarize the *** studies were included in the study,with a total of 1504 patients.A significant association was observed between UCA1 abundance and poor overall survival(OS),and shorter disease-free survival(DFS)for patients with digestive system malignancies,with pooled HR of 2.07(95%CI:1.74-2.47),and of 2.50(95%CI:1.62-3.86).Subgroup analysis and sensitivity analysis suggested the reliability of our *** is suggested that UCA1 abundance may serve as a reliable predictive factor for poor prognosis in patients with digestive system malignancies.

关键词： long noncoding RNAs urothelial carcinoma associated 1 prognosis digestive system tumor meta-analysis

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Open Chromatin Profiling in hiPSC-Derived Neurons Prioritizes Functional noncoding Psychiatric Risk Variants and Highlights Neurodevelopmental Loci

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CELL STEM CELL 2017年第3期21卷 305-+页

作者： Forrest, Marc P. Zhang, Hanwen Moy, Winton McGowan, Heather Leites, Catherine Dionisio, Leonardo E. Xu, Zihui Shi, Jianxin Sanders, Alan R. Greenleaf, William J. Cowan, Chad A. Pang, Zhiping P. Gejman, Pablo V. Penzes, Peter Duan, Jubao Northwestern Univ Dept Physiol Chicago IL 60611 USA NorthShore Univ HealthSyst Ctr Psychiat Genet Evanston IL 60201 USA Rutgers State Univ Dept Neurosci & Cell Biol New Brunswick NJ 08901 USA Rutgers State Univ Child Hlth Inst New Jersey New Brunswick NJ 08901 USA NCI Biostat Branch Div Canc Epidemiol & Genet Bethesda MD 20892 USA Univ Chicago Dept Psychiat & Behav Neurosci Chicago IL 60637 USA Stanford Univ Dept Genet Stanford CA 94305 USA Harvard Univ Dept Stem Cell & Regenerat Biol Cambridge MA 02138 USA

Most disease variants lie within noncoding genomic regions, making their functional interpretation challenging. Because chromatin openness strongly influences transcriptional activity, we hypothesized that cell-type-specific open chromatin regions (OCRs) might highlight disease-relevant noncoding sequences. To investigate, we mapped global OCRs in neurons differentiating from hiPSCs, a cellular model for studying neurodevelopmental disorders such as schizophrenia (SZ). We found that the OCRs are highly dynamic and can stratify GWAS-implicated SZ risk variants. Of the more than 3,500 SZ-associated variants analyzed, we prioritized similar to 100 putatively functional ones located in neuronal OCRs, including rs1198588, at a leading risk locus flanking MIR137. Excitatory neurons derived from hiPSCs with CRISPR/Cas9-edited rs1198588 or a rare proximally located SZ risk variant showed altered MIR137 expression, dendrite arborization, and synapse maturation. Our study shows that noncoding disease variants in OCRs can affect neurodevelopment, and that analysis of open chromatin regions can help prioritize functionally relevant noncoding variants identified by GWAS.

关键词： open chromatin noncoding hiPSC CRISPR/Cas9 schizophrenia ATAC-seq neurodevelopment synapse MIR137 GWAS

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Phylogenomic Resolution of the Phylogeny of Laurasiatherian Mammals: Exploring Phylogenetic Signals within Coding and noncoding Sequences

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GENOME BIOLOGY AND EVOLUTION 2017年第8期9卷 1998-2012页

作者： Chen, Meng-Yun Liang, Dan Zhang, Peng Sun Yat Sen Univ Sch Life Sci Coll Ecol & Evolut State Key Lab Biocontrol Guangzhou Guangdong Peoples R China

The interordinal relationships of Laurasiatherian mammals are currently one of the most controversial questions in mammalian phylogenetics. Previous studies mainly relied on coding sequences (CDS) and seldom used noncoding sequences. Here, by data mining public genome data, we compiled an intron data set of 3,638 genes (all introns from a protein-coding gene are considered as a gene) (19,055,073 bp) and a CDS data set of 10,259 genes (20,994,285 bp), covering all major lineages of Laurasiatheria (except Pholidota). We found that the intron data contained stronger and more congruent phylogenetic signals than the CDS data. In agreement with this observation, concatenation and species-tree analyses of the intron data set yielded well-resolved and identical phylogenies, whereas the CDS data set produced weakly supported and incongruent results. Further analyses showed that the phylogeny inferred from the intron data is highly robust to data subsampling and change in outgroup, but the CDS data produced unstable results under the same conditions. Interestingly, gene tree statistical results showed that the most frequently observed gene tree topologies for the CDS and intron data are identical, suggesting that the major phylogenetic signal within the CDS data is actually congruent with that within the intron data. Our final result of Laurasiatheria phylogeny is (Eulipotyphla,((Chiroptera, Perissodactyla),(Carnivora, Cetartiodactyla))), favoring a close relationship between Chiroptera and Perissodactyla. Our study 1) provides a well-supported phylogenetic framework for Laurasiatheria, representing a step towards ending the long-standing "hard" polytomy and 2) argues that intron within genome data is a promising data resource for resolving rapid radiation events across the tree of life.

关键词： phylogenomics phylogeny intron noncoding data subsampling Laurasiatheria

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Exploring prognostic potential of long noncoding RNAs in colorectal cancer based on a competing endogenous RNA network

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World Journal of Gastroenterology 2020年第12期26卷 1298-1316页

作者： Zhi-Dong Yang Hui Kang Department of Laboratory Medicine The First Affiliated Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina

BACKGROUND Colorectal cancer(CRC)is one of the most prevalent tumors ***,long noncoding RNAs(lncRNAs)have been shown to influence tumorigenesis and tumor progression by acting as competing endogenous RNAs(ceRNAs).It is difficult to extract prognostic lncRNAs and useful bioinformation from most ceRNA networks constructed *** To construct a prognostic related ceRNA regulatory network and lncRNA related signature based on risk score in *** RNA transcriptome profile and clinical information of 506 CRC patients were downloaded from the Cancer Genome Atlas database.R packages and Perl program were used for data *** regression analysis was used for prognostic model *** real-time polymerase chain reaction was used to detect the expression of *** A prognostic-related ceRNA network was constructed,including 9 lncRNAs,44 mRNAs,and 30 *** addition,a four-lncRNA model was constructed using multivariate Cox regression analysis,which could be an independent prognostic model in *** risk score for each patient was calculated,and the 506 patients were divided into high and low-risk groups(253 for each group)based on the median risk *** results of the survival analysis showed that patients with a high-risk score had a poor survival ***,the predictive value of the four-lncRNA model was evaluated in *** survival probabilities could be better predicted when combing the risk score and clinical *** Set Enrichment Analysis results verified that a number of cancer-related signaling pathways were enriched with a high-risk score in ***,we validated a novel lncRNA(LINC00488)using quantitative real-time polymerase chain reaction in 22 paired CRC patient tumor tissues compared to adjacent non-tumor *** The four-lncRNA model could give better predictive value for CRC *** understanding of the lncRNA-related ceRNA regulatory mechanism coul

关键词： Colorectal cancer Long noncoding RNA miRNA mRNA Transcription factor Competing endogenous RNA Survival

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RNAdb -: a comprehensive mammalian noncoding RNA database

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NUCLEIC ACIDS RESEARCH 2005年第Database issue期33卷 D125-D130页

作者： Pang, KC Stephen, S Engström, PG Tajul-Arifin, K Chen, WS Wahlestedt, C Lenhard, B Hayashizaki, Y Mattick, JS Univ Queensland Inst Mol Biosci ARC Special Res Ctr Funct & Appl Genom Brisbane Qld 4072 Australia Austin & Repatriat Med Ctr Ludwig Inst Canc Res Tcell Lab Melbourne Vic 3084 Australia Karolinska Inst Ctr Genom & Bioinformat S-17177 Stockholm Sweden RIKEN Genom Sci Ctr Lab Genome Explorat Res Grp Yokohama Kanagawa 2300045 Japan

In recent years, there have been increasing numbers of transcripts identified that do not encode proteins, many of which are developmentally regulated and appear to have regulatory functions. Here, we describe the construction of a comprehensive mammalian noncoding RNA database (RNAdb) which contains over 800 unique experimentally studied noncoding RNAs (ncRNAs), including many associated with diseases and/or developmental processes. The database is available at http://***. ***/RNAdb and is searchable by many criteria. It includes microRNAs and snoRNAs, but not infrastructural RNAs, such as rRNAs and tRNAs, which are catalogued elsewhere. The database also includes over 1100 putative antisense ncRNAs and almost 20000 putative ncRNAs identified in high-quality murine and human cDNA libraries, with more to be added in the near future. Many of these RNAs are large, and many are spliced, some alternatively. The database will be useful as a foundation for the emerging field of RNomics and the characterization of the roles of ncRNAs in mammalian gene expression and regulation.

关键词： .transcripts rRNAs tRNAs noncoding snoRNAs RNA database RNAdb antisense ncRNAs

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