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The long non-coding RNA DANA2 positively regulates drought tolerance by recruitingERF84 to promote JMJ29-mediated histone demethylation

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Molecular Plant 2023年第8期16卷 1339-1353页

作者： Pengxiang Zhang Reqing He Jun Yang Jingjing Cai Zhipeng Qu Rongxin Yang Jinbao Gu Zhen-Yu Wang David LAdelson Youlin Zhu Xiaofeng Cao Dong Wang Key Laboratory of Molecular Biology and Gene Engineering in Jiangxi Province College of Life ScienceNanchang UniversityJiangxi 330031China State Key Laboratory of Plant Genomics and National Center for Plant Gene Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100039China Department of Molecular and Biomedical Science School of Biological SciencesThe University of AdelaideAdelaideSA 5005Australia Institute of Nanfan&Seed Industry Guangdong Academy of SciencesGuangdong 510316China

Tens of thousands of long non-coding RNAs have been uncovered in plants,but few of them have been comprehensively studied for their biological function and molecular mechanism of their mode of action.Here,we show that the Arabidopsis long non-coding RNA DANA2 interacts with an AP2/ERF transcription factor ERF84 in the cell nucleus and then affects the transcription of JMJ29 that encodes a Jumonji C domain-containing histone H3K9 demethylase.Both RNA sequencing(RNA-seq)and genetic analyses demonstrate that DANA2 positively regulates drought stress responses through JMJ29.JMJ29 positively regulates the expression of ERF15 and GOLS2 by modulation of H3K9me2 demethylation.Accordingly,mutation of JMJ29 causes decreased ERF15 and GOLS2 expression,resulting in impaired drought tolerance,in agreement with drought-sensitive phenotypes of dana2 and erf84 mutants.Taken together,these results demonstrate that DANA2 is a positive regulator of drought response and works jointly with the transcriptional activator ERF84 to modulate JMJ29 expression in plant response to drought.

关键词： long non-coding RNA H3K9 demethylase transcription factor drought response

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KaKs_Calculator 3.0:Calculating Selective Pressure on coding and non-coding Sequences

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Genomics, Proteomics & Bioinformatics 2022年第3期20卷 536-540页

作者： Zhang Zhang National Genomics Data Center Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China University of Chinese Academy of Sciences Beijing 100049China

KaKs_Calculator 3.0 is an updated toolkit that is capable of calculating selective pressure on both coding and non-coding sequences.Similar to the nonsynonymous/synonymous substitution rate ratio for coding sequences,selection on non-coding sequences can be quantified as the ratio of non-coding nucleotide substitution rate to synonymous substitution rate of adjacent coding sequences.As testified on empirical data,KaKs_Calculator 3.0 shows effectiveness to detect the strength and mode of selection operated on molecular sequences,accordingly demonstrating its great potential to achieve genome-wide scan of natural selection on diverse sequences and identification of potentially functional elements at a whole-genome scale.The package of KaKs_Calculator 3.0 is freely available for academic use only at https://***/biocode/tools/BT000001.

关键词： KaKs_Calculator Selective pressure Substitution coding non-coding

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Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第2期25卷 220-232页

作者： Jing-Xian Gu Xing Zhang Run-Chen Miao Xiao-Hong Xiang Yu-nong Fu Jing-Yao Zhang Chang Liu Kai Qu Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi’an Jiaotong University

BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival(OS) of HCC, but the results varied. Thus,more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival(RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator(LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas(TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2 J4, EIF3 J-AS1,SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio(HR) being 1.807(95%CI[confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples(P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomogr

关键词： Long non-coding RNAs Hepatocellular carcinoma Prognostic signature Recurrence-free survival Least absolute shrinkage and selection operator

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Effects of long non-coding RNA Opa-interacting protein 5 antisense RNA 1 on colon cancer cell resistance to oxaliplatin and its regulation of micro RNA-137

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World Journal of Gastroenterology 2020年第13期26卷 1474-1489页

作者： Jing Liang Xiao-Feng Tian Wei Yang Department of Gastrointestinal Surgery China-Japan Union Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Department of Hepatopancreatobiliary Surgery China-Japan Union Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina

BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seriously affect the prognosis of patients.Therefore,this study investigated the mechanism of Opainteracting protein 5 antisense RNA 1(OIP5-AS1)on L-OHP resistance by determining the expression of OIP5-AS1 and micro RNA-137(miR-137)in CC cells and the effects on L-OHP resistance,with the goal of identifying new targets for the treatment of CC.AIM To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.METHODS A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled,and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined.The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated.Resistance to L-OHP was induced in CC cells,and their activity was determined and evaluated using cell counting kit-8.Flow cytometry was used to analyze the apoptosis rate,Western blot to determine the levels of apoptosisrelated proteins,and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.RESULTS OIP5-AS1 was up-regulated in CC tissues and cells,while miR-137 was downregulated in CC tissues and cells.OIP5-AS1 was inversely correlated with miR-137(P<0.001).Silencing OIP5-AS1 expression significantly hindered the proliferation,invasion and migration abilities of CC cells and markedly increased the apoptosis rate.Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate.Moreover,silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to LOHP.OIP5-AS1 targetedly inhibited miR-

关键词： Long non-coding RNA Opa-interacting protein 5 antisense RNA 1 Micro RNA-137 Colon cancer Drug resistance Oxaliplatin Biological behavior

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Long non-coding RNA LncKdm2b regulates cortical neuronal differentiation by cis-activating Kdm2b

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Protein & Cell 2020年第3期11卷 161-186页

作者： Wei Li Wenchen Shen Bo Zhang Kuan Tian Yamu Li Lili Mu Zhiyuan Luo Xiaoling Zhong Xudong Wu Ying Liu Yan Zhou College of Life Sciences Renmin Hospital of Wuhan UniversityMedical Research Institute at School of MedicineWuhan UniversityWuhan 430072China Department of Cell Biology Tianjin Medical UniversityQixiangtai Road 22Tianjin 300070China

The mechanisms underlying spatial and temporal control of cortical neurogenesis of the brain are largely elusive.Long non-coding RNAs(lncRNAs)have emerged as essential cell fate regulators.Here we found LncKdm2b(also known as Kancr),a lncRNA divergently transcribed from a bidirectional promoter of Kdm2b,is transiently expressed during early differentiation of cortical projection neurons.Interestingly,Kdm2b’s transcription is positively regulated in cis by LncKdm2b,which has intrinsic-activating function and facilitates a permissive chromatin environment at the Kdm2b’s promoter by associating with hnRNPAB.Lineage tracing experiments and phenotypic analyses indicated LncKdm2b and Kdm2b are crucial in proper differentiation and migration of cortical projection neurons.These observations unveiled a lncRNA-dependent machinery in regulating cortical neuronal differentiation.

关键词： long non-coding RNA neuronal differentiation cerebral cortex KDM2B divergent lncRNA

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Long non-coding RNA HOTAIRM1 promotes proliferation and inhibits apoptosis of glioma cells by regulating the miR-873-5p/ZEB2 axis

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Chinese Medical Journal 2020年第2期133卷 174-182页

作者： Yi-Hai Lin Liang Guo Feng Yan Zhang-Qi Dou Qian Yu Gao Chen Department of Neurosurgery Zhejiang Tongde HospitalHangzhouZhejiang 310012China Department of Neurosurgery Second Affiliated Hospital of Zhejiang UniversitySchool of MedicineZhejiang UniversityHangzhouZhejiang 310016China

Background:Glioblastoma is one of the most common malignant brain tumors.Conventional clinical treatment of glioblastoma is not sufficient,and the molecular mechanism underlying the initiation and development of this disease remains unclear.Our study aimed to explore the expression and function of miR-873a-5p in glioblastoma and related molecular mechanism.Methods:We analyzed the most dysregulated microRNAs from the Gene Expression Omnibus(GEO)database and examined the expression of miR-873-5p in 20 glioblastoma tissues compared with ten normal brain tissues collected in the Zhejiang Tongde Hospital.We then overexpressed or inhibited miR-873-5p expression in U87 glioblastoma cell lines and analyzed the phenotype using the cell counting kit-8 assay,wound healing assay,and apoptosis.In addition,we predicted upstream and downstream genes of miR-873-5p in glioblastoma using bioinformatics analysis and tested our hypothesis in U87 cells using the luciferase reporter gene assay and Western blotting assay.The differences between two groups were analyzed by Student’s t test.The Kruskal-Wallis test was used for the comparison of multiple groups.A Pnon-coding RNA HOTAIRM1 was found to act as a sponge of miR-873-5p to activate ZEB2 expression in U87 cells.Conclusions:We uncovered a novel HOTAIRM1/miR-873-5p/ZEB2 axis in glioblastoma cells,providing new insight into glioblastoma progression and a theoretical basis for the treatment of glioblastoma.

关键词： MicroRNA Long non-coding RNA ZEB2 Glioblastoma

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Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets

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World Journal of Gastrointestinal Oncology 2019年第11期11卷 983-997页

作者： Zi-Lin Huang Wang Li Qi-Feng Chen Pei-Hong Wu Lu-Jun Shen Department of Medical Imaging and Interventional Radiology Sun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangzhou 510060Guangdong ProvinceChina

BACKGROUND Hepatitis B virus,together with hepatitis C virus,has been recognized as the leading causes of hepatocellular carcinoma(HCC).Long non-coding RNAs(lncRNAs)have been suggested in increasing studies to be the potential prognostic factors for HCC.However,the role of combined application of lncRNAs in estimating overall survival(OS)for hepatitis virus positive HCC(VHCC)is uncertain.AIM To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction.METHODS The expression patterns of lncRNAs,as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database.The R package was adopted to obtain the differentially expressed lncRNAs(DElncRNAs).LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis,so as to construct a least absolute shrinkage and selection operator(LASSO)model.Subsequently,the constructed lncRNA signature was developed and validated.Afterwards,the prognostic nomogram was established,which combined the as-established lncRNA signature as well as the clinical features.Meanwhile,subgroup analysis stratified by the virus type was also performed.Finally,the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly coexpressed genes.RESULTS A total of 1420 DElncRNAs were identified,among which 406 were significant in univariate Cox regression analysis.LASSO regression confirmed 8 out of the 406 lncRNAs,including AC005722.2,AC107959.3,AL353803.1,AL589182.1,AP000844.2,AP002478.1,FLJ36000,and NPSR1-AS1.Then,the prognostic risk score was calculated.Our results displayed a significant association between the risk model and the OS of VHCC[hazard ratio=1.94,95%confidence interval(CI):1.61-2.34,log-rank P=2e-10].The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC.Furthermore,a nomogram was plotted,and the concordance index of internal validation was 0.763(95%CI:0.700-0.826).Moreov

关键词： Long non-coding RNAs Hepatitis virus Hepatocellular carcinoma Prognostic signature Least absolute shrinkage and selection operator

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Long non-coding RNA: The functional regulator of mesenchymal stem cells

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World Journal of Stem Cells 2019年第3期11卷 167-179页

作者： Zhong-Yu Xie Peng Wang Yan-Feng Wu Hui-Yong Shen Department of Orthopedics The Eighth Affiliated Hospital Sun Yat-sen University Center for Biotherapy Sun Yat-sen Memorial Hospital Sun Yat-sen University

Mesenchymal stem cells(MSCs) are a subset of multipotent stroma cells residing in various tissues of the body. Apart from supporting the hematopoietic stem cell niche, MSCs possess strong immunoregulatory ability and multiple differentiation potentials. These powerful capacities allow the extensive application of MSCs in clinical practice as an effective treatment for diseases.Therefore, illuminating the functional mechanism of MSCs will help to improve their curative effect and promote their clinical use. Long noncoding RNA(LncRNA) is a novel class of noncoding RNA longer than 200 nt. Recently,multiple studies have demonstrated that LncRNA is widely involved in growth and development through controlling the fate of cells, including MSCs. In this review, we highlight the role of LncRNA in regulating the functions of MSCs and discuss their participation in the pathogenesis of diseases and clinical use in diagnosis and treatment.

关键词： Mesenchymal stem cells Long non-coding RNA Regulator Multipotent stroma cells

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non-coding RNAs in cancers with chromosomal rearrangements:the signatures,causes,functions and implications

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Journal of Molecular Cell Biology 2019年第10期11卷 886-898页

作者： Cai Han Lin-Yu Sunf Wen-Tao Wang Yu-Meng Sun Yue-Qin Chen MOE Key Laboratory of Gene Function and Regulation State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China

Chromosomal translocation leads to the juxtaposition of two otherwise separate DNA loci,which could result in gene fusion.These rearrangements at the DNA level are catastrophic events and often have causal roles in tumorigenesis.The oncogenic DNA messages are transferred to RNA molecules,which are in most cases translated into cancerous fusion proteins.Gene expression programs and signaling pathways are altered in these cytogenetically abnormal contexts.Notably,non-toding RNAs have attracted increasing attention and are believed to be tightly associated with chromosome-rearranged cancers.These RNAs not only function as modulators in downstream pathways but also directly affect chromosomal translocation or the associated products.This review summarizes recent research advances on the relationship between non-coding RNAs and chromosomal translocations and on diverse functions of non-coding RNAs in cancers with chromosomal rearrangements.

关键词： chromosomal translocation non-coding RNA fusion protein gene regulation non-coding fusion transcript

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Functional impacts of non-coding RNA processing on enhancer activity and target gene expression

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Journal of Molecular Cell Biology 2019年第10期11卷 868-879页

作者： Evgenia Ntini Annalisa Marsico Max Planck Institute for Molecular Genetics 14195BerlinGermany Free University Berlin 14195BerlinGermany Institute of Computational Biology Helmholtz Zentrum MunchenMunchenGermany

Tight regulation of gene expression is orchestrated by enhancers.Through recent research advancements,it is becoming clear that enhancers are not solely distal regulatory elements harboring transcription factor binding sites and decorated with specific histone marks,but they rather display sign atures of active transcription,showingdistinct degrees oftranscription unit organization.Thereby,a substantial fraction of enhancers give rise to different species of non-coding RNA transcripts with an unprecedented range of potential functions.In this review,we bring together data from recent studies indicating that non-coding RNA transcription from active enhancers,as well as enhancer-produced long non-coding RNA transcripts,may modulate or define the functional regulatory potential ofthe cognate enhancer.In addition,we summarize supporting evidence that RNA processing ofthe enhancer-associated long non-coding RNA transcripts may constitute an additional layer of regulation of enhancer activity,which contributes to the control and final outcome of enhancer-targeted gene expression.

关键词： transcription enhancer RNA processing cotranscriptional RNA splicing chromatin long non-coding RNA(IncRNA)

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