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World Journal of Clinical Cases 2018年第5期6卷 64-73页

作者： Farzam Vaziri Samira Tarashi Abolfazl Fateh Seyed Davar Siadat Microbiology Research Center Pasteur Institute of Iran Department of Mycobacteriology and Pulmonary Research Pasteur Institute of Iran

Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.

关键词： Helicobacter pylori Epigenetic Virulence factor non-coding RNAs Host pathogen interactions

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

Long non-coding RNA highly up-regulated in liver cancer promotes exosome secretion

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World Journal of Gastroenterology 2019年第35期25卷 5283-5299页

作者： Shun-Qi Cao Hong Zheng Bao-Cun Sun Zheng-Lu Wang Tao Liu Dong-Hui Guo Zhong-Yang Shen Tianjin First Central Hospital Clinic Institute Tianjin Medical University Tianjin 300070 China Department of Organ Transplantation Tianjin First Central Hospital Tianjin 300192 China Department of Pathology Tianjin Medical University Tianjin 300070 China Department of Pathology Tianjin First Central Hospital Tianjin 300192 China NHC Key Laboratory of Critical Care Medicine Tianjin First Central Hospital Tianjin 300192 China

BACKGROUND Highly upregulated in liver cancer (HULC) is a long non-coding RNA (lncRNA) which has recently been identified as a key regulator in hepatocellular carcinoma (HCC) progression. However, its role in the secretion of exosomes from HCC cells remains unknown. AIM To explore the mechanism by which HULC promotes the secretion of exosomes from HCC cells. METHODS Serum and liver tissue samples were collected from 30 patients with HCC who had not received chemotherapy, radiotherapy, or immunotherapy before surgery. HULC expression in serum exosomes and liver cancer tissues of patients was measured, and compared with the data obtained from healthy controls and tumor adjacent tissues. The effect of HULC upregulation in HCC cell lines and the relationship between HULC and other RNAs were studied using qPCR and dualluciferase reporter assays. Nanoparticle tracking analysis was performed to detect the quantity of exosomes.RESULTS HULC expression in serum exosomes of patients with HCC was higher than that in serum exosomes of healthy controls, and HULC levels were higher in liver cancer tissues than in tumor adjacent tissues. The expression of HULC in serum exosomes and liver cancer tissues correlated with the tumor-node-metastasis (TNM) classification, and HULC expression in tissues correlated with that in serum exosomes. Upregulation of HULC promoted HCC cell growth and invasion and repressed apoptosis. Notably, it also facilitated the secretion of exosomes from HCC cells. Moreover, qPCR assays showed that HULC repressed microRNA-372-3p (miR-372-3p) expression. We also identified Rab11a as a downstream target of miR-372-3p. Dual-luciferase reporter assays suggested that miR-372-3p could directly bind both HULC and Rab11a. CONCLUSION Our findings illustrate the importance of the HULC/miR-372-3p/Rab11a axis in HCC and provide new insights into the molecular mechanism regulating the secretion of exosomes from HCC cells.

关键词： Long non-coding RNA Exosomes Hepatocellular carcinoma miR-372-3p Rab11a

Behind the curtain of non-coding RNAs; long non-coding RNAs regulating hepatocarcinogenesis

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World Journal of Gastroenterology 2018年第5期24卷 549-572页

作者： Aya El Khodiry Menna Afify Hend M El Tayebi Genetic Pharmacology Research Group Clinical Pharmacy Unit department of Pharmacology and toxicology faculty of Pharmacy and biotechnology German University in Cairo

Hepatocellular carcinoma(HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs(lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of m RNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.

关键词： tumor suppressor genes oncogenes Long non-coding RNAs proliferation hepatocellular carcinoma metastasis

Long non-coding RNAs as novel diagnostic and therapeutic targets in kidney disease

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Chronic Diseases and Translational Medicine 2019年第4期5卷 252-257页

作者： Qin Zhou Wei Chen Xue-Qing Yu Department of Nephrology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China National Health Commission Key Laboratory of Nephrology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China Guangdong Provincial Key Laboratory of Nephrology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China Guangdong General Hospital GuangzhouGuangdong510080China

Long non-coding RNAs(IncRNAs)have critical roles in the development of many diseases including kidney disease.An increasing number of studies have shown that IncRNAs are involved in kidney development and that their dysregulation can result in distinct disease processes,including acute kidney injury(AKI),chronic kidney disease(CKD),and renal cell carcinoma(RCC).Understanding the roles of IncRNAs in kidney disease may provide new diagnostic and therapeutic opportunities in the clinic.This review provides an overview of IncRNA characteristics,biological function and discusses specific studies that provide insight into the function and potential application of IncRNAs in kidney disease treatment.

关键词： Long non-coding RNAs Kidney disease Renal inflammation Renal fibrosis Diabetic nephritis Renal cell carcinoma

Hide and Seek: Protein-coding Sequences Inside ‘‘non-coding” RNAs

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Genomics, Proteomics & Bioinformatics 2016年第4期14卷 179-180页

作者： Daniel Oehler Jan Haas Institute for Cardiomyopathies Department of Internal Medicine IIIUniversity of Heidelberg69120 HeidelbergGermany German Centre for Cardiovascular Research(DZHK) Heidelberg/MannheimGermany

Calcium homeostasis is crucial for muscle contractilityMuscle cells are critically dependent on calcium homeostasis. Without having the right amount of calcium ions just on the spot and coordinated in between muscle cells, no contraction can take place. Therefore, calcium homeostasis is one of the critical regulatory mechanisms in all muscle cells, including skeletal muscle and heart [1,2]. Ca2＋ adenosine triphosphatase the relaxation of muscle cells Sarco-endoplasmic reticulum （SERCA） is responsible for by pumping Ca2＋ into the sarcoplasmic reticulum （SR） .

关键词： SERCA RNAs Hide and Seek non-coding Protein-coding Sequences Inside

Silencing of long non-coding RNA CCHE1 inhibits the ovarian cancer SKOV3 cell invasion and migration and inactivates the p38-MAPK signaling pathway

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BIOCELL 2020年第3期44卷 345-351页

作者： HONGWEI CHEN XUAN SONG HEMEI LI Department of Gynecology and Obstetrics the Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430014China

Ovarian cancer(OC)is a major cause of cancer-related deaths among gynaecologicalmalignancies.Emerging studies suggest that the long non-coding RNA(lncRNA)may be the potential biomarker for the diagnosis and prognosis of the cancer.The current study was carried out to investigate the role of lncRNA CCHE1 silencing in OC cell invasion and migration.Expression of lncRNA CCHE1 in normal ovarian cell Hose and OC cell lines HO 8910,A2780 and SKOV3 was detected.LncRNA were transfected with siRNA,and then the proliferation of cells was detected by using MTT assay.Cell invasion and migration was measured by using Transwell assay and scratch test,respectively.The protein levels of E-cadherin,N-cadherin,ERK,p38-MAPK and the phosphorylation of ERK and p38-MAPK in cells after siRNA transfection were detected by using Western blot analysis.Consequently,lncRNA CCHE1 expression was highly expressed in OC cell lines,especially in SKOV3 cells.siRNA1,siRNA2 and siRNA3 all decreased.lncRNA CCHE1 expression in SKOV3 cells and siRNA2 showed the best silencing efficacy.Silencing of lncRNA CCHE1 decreased proliferation,invasion and migration,and reduced the protein levels of N-cadherin,ERK,p38-MAPK and the phosphorylation of ERK and p38-MAPK,while reducing the protein level of E-cadherin in SKOV3 cells.Collectively,our study proved that the silencing of lncRNA CCHE1 could inhibit SKOV3 cell invasion and migration via inactivating the p38-MAPK signaling pathway.

关键词： Long non-coding RNA CCHE1 Ovarian cancer Invasion Migration

ZokorDB: tissue specific regulatory network annotation for non-coding elements of plateau zokor

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Quantitative Biology 2020年第1期8卷 43-50页

作者： Jingxue Xin Junjun Hao Lang Chen Tao Zhang Lei Li Luonan Chen Wenmin Zhao Xuemei Lu Peng Shi Yong Wang CEMS NCMISMDISAcademy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China State Key Laboratory of Genetic Resources and Evolution Laboratory of Evolutionary and Functional GenomicsKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Key Laboratory of Systems Biology Innovation Center for Cell Signaling NetworkInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Beijing Institute of Genomics Chinese Academy of SciencesBeijing 100101China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China Department of Statistics Department of Biomedical Data ScienceBio-X ProgramStanford UniversityStanfordCA 94305USA University of Chinese Academy of Sciences Beijing 100049China

Background:Plateau zokor inhabits in sealed burrows from 2,000 to 4,200 meters at Qinghai-Tibet Plateau.This extreme living env ironment makes it a great model to study animal adaptation to hypoxia,low temperature,and high carbon dioxide concentration.Methods:We provide an integrated resource,ZokorDB,for tissue specific regulatory network annotation for zokor.ZokorDB is based on a high-quality draft genome of a plateau zokor at 3,300 m and its transcriptional profiles in brain,heart,liver,kidney,and lung.The conserved non-coding elements of zokor are annotated by their nearest genes and upstream transcriptional factor motif binding sites.Results:ZokorDB provides a general draft gene regulatory network(GRN),Le?potential transcription factor(TF)binds to non-coding regulatory elements and regulates the expression of target genes(TG).Furthermore,we refined the GRN by incorporating matched RNA-seq and DNase-seq data from mouse ENCODE project and reconstructed five tissue-specific regulatory networks.Conclusions:A web-based,open-access database is developed for easily searching,visualizing,and downloading the annotation and data.The pipeline of non-coding region annotation for zokor will be useful for other non-model species.ZokorDB is free available at the website(***/zokordb/).

关键词： tissue specific regulatory network non-coding element plateau zokor non-model species

Two non-coding transcripts of toxins from the scorpion But-hus martensii Karsch: Evidence for the existence of NMD in scorpion venom gland cells

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Chinese Science Bulletin 2002年第1期47卷 47-51页

作者： Zhu, SY Li, WX Wuhan Univ Dept Biotechnol Coll Life Sci Wuhan 430072 Peoples R China

Two non-coding transcripts of toxins were iso-lated from the venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch, named BmαTX15-SP and BmTXKβ-SP, respectively. Analysis of nucleotide sequences shows that their 5’ sequences are identical to the 5 ’UTR and upstream open reading frame (ORF) sequences of the cDNAs encoding BmαTX15 and BmTXKb, two toxins from Buthus martensii Karsch. But no detectable homology exists in other regions. Two polyadenylated non-coding transcripts encode multiple short ORFs with no more than 34 amino acid resi-dues. The tailing signal (AATAAA) is situated at 14 or 18 bp downstream from the poly(A). The data of genomic se-quences provides support for Bmα TX15-SP and BmTXK β-SP not deriving from splicing errors of pre- mRNAs. Our finding provides evidence for the existence of non-sense-mediated mRNA decay (NMD) pathway in scorpion venom gland cells.

关键词： Buthus martensii Karsch non-coding transcripts NMD toxins genomic organization.

Construction of a CRISPR-based paired-sgRNA library for chromosomal deletion of long non-coding RNAs

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Quantitative Biology 2020年第1期8卷 31-42页

作者： Minzhen Tao Qiaochu Mu Yurui Zhang Zhen Xie MOE Key Laboratory of Bioinformatics and Bioinformatics Division Center for Synthetic and System BiologyDepartment of AutomationBeijing National Research Center for Information Science and TechnologyTsinghua UniversityBeijing 100084China Zhejiang Tmall Techonogy Co. LtdYuhang DistrictHangzhou 311121China Beiing Syngentech Co..Ltd Zhongguancun Life Science ParkChangping DistrictBeijing 102206China

Background:Derived from an adaptive bacterial immune system,the clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated 9(Cas9)system has shown great potential in high-throughput functional genomic screening,especially for protein-coding genes.However,it is still challenging to apply the similar strategy to study non-coding genomic elements such as long non-coding RNAs(lncRNAs)or clusters of microRNAs,because short insertions or deletions may not be sufficient to generate loss-of-function phenotypes.Methods:Here,we presented a systematic strategy for designing a CRISPR-based paired-sgRNA library for highthroughput screening in non-coding regions.Due to the abundance of lncRNAs and their diverse regulatory roles in vivo,we repurposed microarray datasets to select 600 highly expressed lncRNAs in non-small-cell lung cancer and designed two schemes for lncRNA deletion with^20 paired-sgRNAs for each lncRNA.Through Golden-Gate assembly,we generated a pooled CRISPR-based library with a total of 12,878 sgRNA pairs.Results:Over 80%of paired-sgRNAs were recovered from final pooled library with a relarively even distribution.Cleavage efficiency of sgRNA pairs was validated through experiments of transient transfection and viral infection.Moreover,randomly selected paired-sgRNAs showed that efficient deletion of genomic DNA could be achieved with a deletion size within the range of 500 to 3000 bp.Conclusions:In summary,we have demonstrated a strategy to design and construct a pooled paired-sgRNA library to generate genomic deletion in the lncRNA regions,validated their deletion efficiency and explored the relationship of deletion efficiency with respect to deletion size.This method would be also suitable for investigation of other uncharacterized non-coding genomic regions in mammalian cells in an efficient and cost-efTective manner.

关键词： CRISPR/Cas9 paired-sgRNA chromosomal deletion non-coding genomic elements lncRNA