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HIF-1α regulation in mammalian hibernators: role of non-coding rna in HIF-1α control during torpor in ground squirrels and bats

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JOUrnaL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMS AND ENVIRONMENTAL PHYSIOLOGY 2012年第6期182卷 849-859页

作者： Maistrovski, Yulia Biggar, Kyle K. Storey, Kenneth B. Carleton Univ Dept Biol Inst Biochem Ottawa ON K1S 5B6 Canada

A potential role for non-coding rnas, miR-106b and antisense hypoxia inducible transcription factor-1 (HIF-1 alpha), in HIF-1 alpha regulation during mammalian hibernation was investigated in two species, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) and the little brown bat (Myotis lucifugus). Both species showed differential regulation of HIF-1 alpha during hibernation. HIF-1 alpha protein levels increased significantly in skeletal muscle of both species when animals entered torpor, as well as in bat liver. HIF-1 alpha mrna levels correlated with the protein increase in bat skeletal muscle and liver but not in squirrel skeletal muscle. Antisense HIF-1 alpha transcripts were identified in skeletal muscle of both hibernators. The expression of antisense HIF-1 alpha was reduced in skeletal muscle of torpid bats compared with euthermic controls, suggesting that release of inhibition by the antisense rna contributes to regulating HIF-1 alpha translation in this tissue during torpor. The expression of miR-106b, a microrna associated with HIF-1 alpha regulation, also decreased during torpor in both skeletal muscle and liver of bats and in ground squirrel skeletal muscle. These data present the first evidence that non-coding rna provides novel post-transcriptional mechanisms of HIF-1 alpha regulation when hibernators descend into deep cold torpor, and also demonstrate that these mechanisms are conserved in two divergent mammalian orders (Rodentia and Chiroptera).

关键词： Hypoxia response HIF-1 alpha Antisense rna non-coding rna Microrna Hibernation

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microrna-29 can regulate expression of the long non-coding rna gene MEG3 in hepatocellular cancer

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ONCOGENE 2011年第47期30卷 4750-4756页

作者： Braconi, C. Kogure, T. Valeri, N. Huang, N. Nuovo, G. Costinean, S. Negrini, M. Miotto, E. Croce, C. M. Patel, T. Mayo Clin Dept Transplantat Jacksonville FL 32224 USA Ohio State Univ Coll Med Columbus OH 43210 USA Ohio State Univ Ohio State Univ Comprehens Canc Ctr Columbus OH 43210 USA Ohio State Univ Dept Pathol Columbus OH 43210 USA Univ Ferrara Dept Expt & Diagnost Med I-44100 Ferrara Italy

The human genome is replete with long non-coding rnas (lncrna), many of which are transcribed and likely to have a functional role. Microarray analysis of 423 000 lncrnas revealed downregulation of 712 (similar to 3%) lncrna in malignant hepatocytes, among which maternally expressed gene 3 (MEG3) was downregulated by 210-fold relative to expression in non-malignant hepatocytes. MEG3 expression was markedly reduced in four human hepatocellular cancer (HCC) cell lines compared with normal hepatocytes by real-time PCR. rna in situ hybridization showed intense cytoplasmic expression of MEG3 in non-neoplastic liver with absent or very weak expression in HCC tissues. Enforced expression of MEG3 in HCC cells significantly decreased both anchorage-dependent and -independent cell growth, and induced apoptosis. MEG3 promoter hypermethylation was identified by methylation-specific PCR and MEG3 expression was increased with inhibition of methylation with either 5-Aza-2-Deoxycytidine, or sirna to DNA Methyltransferase (DNMT) 1 and 3b in HCC cells. Mirna-dependent regulation of MEG3 expression was studied by evaluating the involvement of miR-29, which can modulate DNMT 1 and 3. Overexpression of mir-29a increased expression of MEG3. GTL2, the murine homolog of MEG3, was reduced in liver tissues from hepatocyte-specific miR-29a/b1 knock-out mice compared with wild-type controls. These data show that methylation-dependent tissue-specific regulation of the lncrna MEG3 by miR-29a may contribute to HCC growth and highlight the inter-relationship between two classes of non-coding rna, mirnas and lncrnas, and epigenetic regulation of gene expression. Oncogene (2011) 30, 4750-4756;doi:10.1038/onc.2011.193;published online 30 May 2011

关键词： MEG3 methylation HCC non-coding rna

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Role of non-coding rna in immune microenvironment and anticancer therapy of gastric cancer

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JOUrnaL OF MOLECULAR MEDICINE-JMM 2022年第12期100卷 1703-1719页

作者： Chen, Liqiao Deng, Jingyu Tianjin Med Univ Canc Inst & Hosp Natl Clin Res Ctr Canc Dept Gastr Surg Tianjin 300060 Peoples R China Key Lab Canc Prevent & Therapy Tianjin 300060 Peoples R China Tianjins Clin Res Ctr Canc Tianjin 300060 Peoples R China

Gastric cancer remains one of the cancers with the highest mortality in the world;therefore, it is very important to investigate its pathogenesis to improve the prognosis of gastric cancer patients. Recently, noncoding rnas have become a research hotspot in the field of oncology. These rna molecules play complex roles in the regulation of tumor cells, immune cells, and the tumor microenvironment. Therefore, studying their ability to regulate the gastric cancer immune microenvironment will provide us with a better perspective to understand their potential role in anticancer therapy. In this review, we discuss the regulatory effects of several common noncoding rnas on the immune microenvironment of gastric cancer and their prospects in anticancer therapy to provide some novel insight into the identification of valuable diagnostic markers and improving the prognosis of gastric cancer patients.

关键词： non-coding rna Gastric cancer Immune microenvironment Anticancer therapy Biomarker

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Long non-coding rna Tug1 modulates mitochondrial and myogenic responses to exercise in skeletal muscle

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BMC BIOLOGY 2022年第1期20卷 1-19页

作者： Trewin, Adam J. Silver, Jessica Dillon, Hayley T. Della Gatta, Paul A. Parker, Lewan Hiam, Danielle S. Lee, Yin Peng Richardson, Mark Wadley, Glenn D. Lamon, Severine Deakin Univ Inst Phys Act & Nutr Geelong Vic Australia Deakin Univ Sch Exercise & Nutr Sci Geelong Vic Australia Baker Heart & Diabet Inst Human Integrated Physiol & Sports Cardiol Lab Melbourne Vic Australia Victoria Univ Inst Hlth & Sport iHeS Melbourne Vic Australia Deakin Univ Genom Ctr Sch Life & Environm Sci Fac Sci Engn & Built Environm Waurn Ponds Vic Australia

Background: Mitochondria have an essential role in regulating metabolism and integrate environmental and physiological signals to affect processes such as cellular bioenergetics and response to stress. In the metabolically active skeletal muscle, mitochondrial biogenesis is one important component contributing to a broad set of mitochondrial adaptations occurring in response to signals, which converge on the biogenesis transcriptional regulator peroxisome proliferator-activated receptor coactivator 1-alpha (PGC-1 alpha), and is central to the beneficial effects of exercise in skeletal muscle. We investigated the role of long non-coding rna (lncrna) taurine-upregulated gene 1 (TUG7), which interacts with PGC-1 alpha in regulating transcriptional responses to exercise in skeletal muscle. Results: In human skeletal muscle, TUG1 gene expression was upregulated post-exercise and was also positively correlated with the increase in PGC-1 alpha gene expression (PPARGC1A). Tug 1 knockdown (KD) in differentiating mouse myotubes led to decreased Ppargcla gene expression, impaired mitochondrial respiration and morphology, and enhanced myosin heavy chain slow isoform protein expression. In response to a Ca2+-mediated stimulus, Tug 1 KD prevented an increase in Ppargcla expression. rna sequencing revealed that Tug 1 KD impacted mitochondrial Ca2+ transport genes and several downstream PGC-1 alpha targets. Finally, Tug 1 KD modulated the expression of similar to 300 genes that were upregulated in response to an in vitro model of exercise in myotubes, including genes involved in regulating myogenesis. Conclusions: We found that TUG 1 is upregulated in human skeletal muscle after a single session of exercise, and mechanistically, Tug 1 regulates transcriptional networks associated with mitochondrial calcium handling, muscle differentiation and myogenesis. These data demonstrate that lncrna Tug 1 exerts regulation over fundamental aspects of skeletal muscle biology and response to ex

关键词： Muscle Transcriptome non-coding rna Bioenergetics

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Long non-coding rna TUSC7 inhibits temozolomide resistance by targeting miR-10a in glioblastoma

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CANCER CHEMOTHERAPY AND PHARMACOLOGY 2018年第4期81卷 671-678页

作者： Shang, Chao Tang, Wei Pan, Chen Hu, Xuanhao Hong, Yang China Med Univ Basic Med Coll Dept Neurobiol Shenyang Liaoning Peoples R China China Med Univ Shengjing Hosp Dept Neurosurg Shenyang Liaoning Peoples R China

Human glioblastoma multiforme (GBM) is the most malignant intracranial primary cancer and is associated with high mortality and poor prognosis. This study aimed to investigate the regulatory effects and mechanism of tumor suppressor candidate 7 (TUSC7) gene to malignant proliferation and chemotherapy resistance to temozolomide (TMZ) in glioma cells. The expression of TUSC7 was detected by quantitative real-time PCR. CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry were used to detect cell cycle and cell apoptosis. The expression of MDR1 protein was examined by western blot. rna pull-down assay was applied to confirm the specific combination between TUSC7 and miR-10a. In the present study, we detected low expression of TUSC7 in GBM cells and tissues resistant to TMZ. Upregulation of TUSC7 suppressed both TMZ resistance and expression of multidrug resistance protein 1 (MDR1) in U87TR cells. TUSC7 acted by directly targeting and silencing expression of miR-10a gene, and miR-10a mediated TUSC7-induced inhibition on TMZ resistance in U87TR cells. These findings suggest a negative correlation between TUSC7 expression and TMZ resistance and provide a mechanism and rationale for targeting TUSC7 in the treatment of GBM.

关键词： Glioblastoma multiforme non-coding rna Tumor suppressor candidate 7 Microrna-10a Temozolomide Chemotherapy Resistance

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Comprehensive long non-coding rna expression profiling reveals their potential roles in systemic lupus erythematosus

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CELLULAR IMMUNOLOGY 2017年 319卷 17-27页

作者： Li, Lian-Ju Zhao, Wei Tao, Sha-Sha Li, Jun Xu, Shu-Zhen Wang, Jie-Bing Leng, Rui-Xue Fan, Yin-Guang Pan, Hai-Feng Ye, Dong-Qing Anhui Med Univ Sch Publ Hlth Dept Epidemiol & Biostat 81 Meishan Rd Hefei 230032 Anhui Peoples R China Anhui Prov Key Lab Major Autoimmune Dis Hefei Anhui Peoples R China

Long non-coding rnas can regulate gene transcription, modulate protein function, and act as competing endogenous rna. Yet, their roles in systemic lupus erythematosus remain to be elucidated. We determined the expression profiles of lncrnas in T cells of SLE patients and healthy controls using microarrays. Up to 1935 lncrnas and 1977 mrnas were differentially expressed. QRT-PCR showed downregulated uc001ykl. 1 and ENST00000448942 in SLE patients. Expression of uc001ykl.1 correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein, whereas ENST00000448942 level correlated with ESR and anti-Sm antibodies. Short time-series expression miner analysis revealed some lncrnas whose expressions might correlate with disease activity of SLE patients. coding-non-coding gene coexpression analyses showed differential lncrnas might operate via modulating expressions of their correlated, relevant mrnas in SLE. Differential lncrnas might also function through their cernas. Our study established that the aberrant expression profiles of lncrnas may play a role in SLE and thus warrant further investigation.

关键词： Long non-coding rna Systemic lupus erythematosus non-coding rna Microrna cerna

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Advancing Pan-cancer Gene Expression Survial Analysis by Inclusion of non-coding rna

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rna BIOLOGY 2020年第11期17卷 1666-1673页

作者： Ye, Bo Shi, Jianxin Kang, Huining Oyebamiji, Olufunmilola Hill, Deirdre Yu, Hui Ness, Scott Ye, Fei Ping, Jie He, Jiapeng Edwards, Jeremy Zhao, Ying-Yong Guo, Yan Jiaotong Univ Shanghai Chest Hosp Dept Thorac Surg Shanghai Peoples R China Univ New Mexico Comprehens Canc Ctr Albuquerque NM 87109 USA Vanderbilt Univ Med Ctr Dept Biostat Nashville TN USA Northwest Univ Sch Life Sci Key Lab Resource Biol & Biotechnol Western China Xian Shaanxi Peoples R China

non-coding rnas occupy a significant fraction of the human genome. Their biological significance is backed up by a plethora of emerging evidence. One of the most robust approaches to demonstrate non-coding rna?s biological relevance is through their prognostic value. Using the rich gene expression data from The Cancer Genome Altas (TCGA), we designed Advanced Expression Survival Analysis (AESA), a web tool which provides several novel survival analysis approaches not offered by previous tools. In addition to the common single-gene approach, AESA computes the gene expression composite score of a set of genes for survival analysis and utilizes permutation test or cross-validation to assess the significance of log-rank statistic and the degree of over-fitting. AESA offers survival feature selection with post-selection inference and utilizes expanded TCGA clinical data including overall, disease-specific, disease-free, and progression-free survival information. Users can analyse either protein-coding or non-coding regions of the transcriptome. We demonstrated the effectiveness of AESA using several empirical examples. Our analyses showed that non-coding rnas perform as well as messenger rnas in predicting survival of cancer patients. These results reinforce the potential prognostic value of non-coding rnas. AESA is developed as a module in the freely accessible analysis suite MutEx.

关键词： Cancer survival analysis non-coding rna lincrna pseudogene

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Epigenetic regulation of human non-coding rna gene transcription

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BIOCHEMICAL SOCIETY TRANSACTIONS 2022年第2期50卷 723-736页

作者： Morselli, Marco Dieci, Giorgio Univ Parma Dept Chem Life Sci & Environm Sustainabil Parco Area Sci 23-A I-43124 Parma Italy

Recent investigations on the non-protein-coding transcriptome of human cells have revealed previously hidden layers of gene regulation relying on regulatory non-proteincoding (nc) rnas, including the widespread ncrna-dependent regulation of epigenetic chromatin states and of mrna translation and stability. However, despite its centrality, the epigenetic regulation of ncrna genes has received relatively little attention. In this mini-review, we attempt to provide a synthetic account of recent literature suggesting an unexpected complexity in chromatin-dependent regulation of ncrna gene transcription by the three human nuclear rna polymerases. Emerging common features, like the heterogeneity of chromatin states within ncrna multigene families and their influence on 3D genome organization, point to unexplored issues whose investigation could lead to a better understanding of the whole human epigenomic network.

关键词： chromatin DNA methylation epigenetics non-coding rna rna polymerase

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CCAT1: a pivotal oncogenic long non-coding rna in human cancers

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CELL PROLIFERATION 2016年第3期49卷 255-260页

作者： Xin, Yu Li, Zheng Shen, Jianxiong Chan, Matthew T. V. Wu, William Ka Kei Chinese Acad Med Sci Peking Union Med Coll Hosp Dept Dermatol Beijing 100042 Peoples R China Peking Union Med Coll Beijing 100042 Peoples R China Chinese Acad Med Sci Peking Union Med Coll Hosp Dept Orthoped Surg Beijing 100042 Peoples R China Chinese Univ Hong Kong Dept Anaesthesia & Intens Care Hong Kong 999077 Hong Kong Peoples R China Chinese Univ Hong Kong LKS Inst Hlth Sci State Key Lab Digest Dis Hong Kong 999077 Hong Kong Peoples R China

Long non-coding rnas (lncrnas) compose a group of non-protein-coding rnas - more than 200 nucleotides in length. Recent studies have shown that lncrnas play important roles in different cellular processes, including proliferation, differentiation, migration and invasion. Deregulation of lncrnas has been widely reported in human tumours, in which they are able to function as either oncogenes (on the one hand) or tumour suppressor genes (on the other). Deregulation of CCAT1 (colon cancer-associated transcript-1), an oncogenic lncrna, has been documented in different types of malignancy, such as gastric cancer, colorectal cancer and hepatocellular carcinoma. In this regard, enforced expression of CCAT1 exerts potent tumorigenic effects by promoting cell proliferation, invasion and migration. Recent evidence has also shown that CCAT1 may serve as a prognostic cancer biomarker. In this review, we provide an overview of current evidence relating to the role and biological function of CCAT1 in tumour development.

关键词： COLON cancer non-coding rna CANCER cell migration GENETIC transcription CANCER cells -- Proliferation CANCER invasiveness

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Role of long non-coding rna ELFN1-AS1 in carcinogenesis

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DISCOVER ONCOLOGY 2024年第1期15卷 74页

作者： Hajiesmailpoor, Zanyar Fayazi, Alireza Teymouri, Mohammadhossein Tabnak, Peyman Tabriz Univ Med Sci Fac Med Tabriz Iran Islamic Azad Univ Najafabad Branch Dept Gynecol Esfahan Iran Univ Pavia Dept Biol & Biotechnol Pavia Italy

As one of the leading causes of death worldwide, cancer significantly burdens patients and the healthcare system. The role of long non-protein coding rnas (lncrnas) in carcinogenesis has been extensively studied. The lncrna ELFN1-AS1 was discovered recently, and subsequent studies have revealed its aberrantly high expression in various cancer tissues. In vitro and in vivo experiments have consistently demonstrated the close association between increased ELFN1-AS1 expression and malignant tumor characteristics, particularly in gastrointestinal malignancies. Functional assays have further revealed the mechanistic role of ELFN1-AS1 as a competitive endogenous rna for micrornas, inducing tumor growth, invasive features, and drug resistance. Additionally, the investigation into the clinical implication of ELFN1-AS1 has demonstrated its potential as a diagnostic, therapeutic, and, notably, prognostic marker. This review provides a comprehensive summary of evidence regarding the involvement of ELFN1-AS1 in cancer initiation and development, highlighting its clinical significance.

关键词： lncrna microrna non-coding rna Cancer Prognosis

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