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Single-nucleotide polymorphism rs4142441 and MYC co-modulated long non-coding rna OSER1-AS1 suppresses non-small cell lung cancer by sequestering ELAVL1

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CANCER SCIENCE 2021年第6期112卷 2272-2286页

作者： Xie, Weijia Wang, Youhao Zhang, Yao Xiang, Ying Wu, Na Wu, Long Li, Chengying Cai, Tongjian Ma, Xiangyu Yu, Zubin Bai, Li Li, Yafei Third Mil Med Univ Army Med Univ Coll Prevent Med Dept Epidemiol 30 Gaotanyan St Chongqing 400038 Peoples R China Third Mil Med Univ Army Med Univ Xinqiao Hosp Dept Thorac Surg Chongqing Peoples R China Third Mil Med Univ Army Med Univ Xinqiao Hosp Dept Resp Dis Chongqing Peoples R China

Single-nucleotide polymorphisms (SNP) and long non-coding rnas (lncrnas) have been involved in the process of lung cancer. Following clues given by lung cancer risk-associated SNP, we aimed to find novel functional lncrnas as candidate targets in lung cancer. We identified a lncrna Oxidative Stress Responsive Serine Rich 1 Antisense rna 1 (OSER1-AS1) through a lung cancer risk-associated SNP rs4142441. OSER1-AS1 was down-regulated in tumor tissue and its low expression was significantly associated with poor overall survival among non-smokers in non-small cell lung cancer (NSCLC) patients. Gain- and loss-of-function studies showed that OSER1-AS1 acted as a tumor suppressor by inhibiting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays and a metastasis mouse model confirmed that OSER1-AS1 suppressed tumor growth and metastasis in vivo. The promoter of OSER1-AS1 was repressed by MYC, and the 3 '-end of OSER1-AS1 was competitively targeted by microrna hsa-miR-17-5p and rna-binding protein ELAVL1. Our results indicated that OSER1-AS1 exerted tumor-suppressive functions by acting as an ELAVL1 decoy to keep it away from its target mrnas. Our findings characterized OSER1-AS1 as a new tumor-suppressive lncrna in NSCLC, suggesting that OSER1-AS1 may be suitable as a potential biomarker for prognosis, and a potential target for treatment.

关键词： ELAVL1 long non‐ coding rna miR‐ 17‐ 5p non‐ small cell lung cancer OSER1‐ AS1

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Non-coding rna Identification in Osteonecrosis of the Femoral Head Using Competitive Endogenous rna Network Analysis

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ORTHOPAEDIC SURGERY 2021年第3期13卷 1067-1076页

作者： Han, Ning Li, Zengchun Tongji Univ Dept Emergency Trauma Surg Shanghai East Hosp 150 Jimo Rd Shanghai 200120 Peoples R China

Objective To investigate the regulatory network of long non-coding rna (lncrna) as competing endogenous rnas (cernas) in osteonecrosis of the femoral head (ONFH). Methods The gene expression profile GSE74089 of ONFH and microrna (mirna) expression profile of GSE89587 were obtained from the Gene Expression Omnibus (GEO) database. The GSE74089 contained four ONFH samples and four controls. The GSE89587 included 10 ONFH samples and 10 control samples. The differentially expressed lncrnas (DE-lncrnas) and DE-mrnas between ONFH group and control group were identified from GSE74089 using the limma package based on criteria of adjusted P value <0.05 and |log fold change (FC)| >= 2. The DEmirnas between ONFH group and control group were screened from GSE89587 on the basis of adjusted P value <0.05. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for DE-mrnas were analyzed using DAVID 6.7 and GSEA 3.0, respectively. Coexpressed lncrna-mrna pairs were identified by *** method in R based on the criteria of adjusted P value <0.01 and |r| >= 0.9. A cerna network was constructed and visualized using cytoscape 3.7.0 by integrating the DE-lncrna, DE-mirna, and DEmrna data. The key mrnas and lncrnas in the cerna network were further validated in an independent dataset of GSE123568. Results Based on our analysis, a total of 28 DE-lncrnas, 1403 DE-mrnas, and 134 DE-mirnas were identified, respectively. The DE-mrnas were significantly enriched in the function of "skeletal system development," "collagen fibril organization," "blood vessel development," and "regulation of nervous system development." Besides, 72 KEGG pathways, including eight active pathways and 64 suppressed pathways were identified, including which immune pathway was the most significantly activated one and which ribosome-related function was the most suppressed. A co-expression network including 161 DE-mrnas and 16 DE-lncrnas was built. Highly connected nodes were identified among l

关键词： Competing endogenous rnas Long non‐ coding rna Osteonecrosis of the femoral head

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Emerging role of non-coding rna in health and disease

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METABOLIC BRAIN DISEASE 2021年第6期36卷 1119-1134页

作者： Bhatti, Gurjit Kaur Khullar, Naina Sidhu, Inderpal Singh Navik, Uma Shanker Reddy, Arubala P. Reddy, P. Hemachandra Bhatti, Jasvinder Singh Chandigarh Univ Univ Inst Appl Hlth Sci Dept Med Lab Technol Mohali Punjab India Mata Gujri Coll Dept Zool Fatehgarh Sahib Punjab India Sri Guru Gobind Singh Coll Dept Zool Chandigarh India Cent Univ Punjab Dept Pharmacol Bathinda India Texas Tech Univ Nutr Sci Lubbock TX 79409 USA Texas Tech Univ Hlth Sci Ctr Neurosci & Pharmacol Lubbock TX 79430 USA Texas Tech Univ Hlth Sci Ctr Dept Internal Med Lubbock TX 79430 USA Texas Tech Univ Hlth Sci Ctr Dept Neurol Sch Med Lubbock TX 79430 USA Texas Tech Univ Hlth Sci Ctr Publ Hlth Dept Grad Sch Biomed Sci Lubbock TX 79430 USA Texas Tech Univ Hlth Sci Ctr Dept Speech Language & Hearing Sci Sch Hlth Profess Lubbock TX 79430 USA Texas Tech Univ Hlth Sci Ctr Cell Biol & Biochem Neurosci & PharmacolNeurolPubl HlthSch Hlth Pr 3601 4th St Lubbock TX 79430 USA Cent Univ Punjab Sch Hlth Sci Dept Human Genet & Mol Med Bathinda India

Human diseases have always been a significant turf of concern since the origin of mankind. It is cardinal to know the cause, treatment, and cure for every disease condition. With the advent and advancement in technology, the molecular arena at the microscopic level to study the mechanism, progression, and therapy is more rational and authentic pave than a macroscopic approach. Non-coding rnas (ncrnas) have now emerged as indispensable players in the diagnosis, development, and therapeutics of every abnormality concerning physiology, pathology, genetics, epigenetics, oncology, and developmental diseases. This is a comprehensive attempt to collate all the existing and proven strategies, techniques, mechanisms of genetic disorders including Silver Russell Syndrome, Fascio- scapula humeral muscular dystrophy, cardiovascular diseases (atherosclerosis, cardiac fibrosis, hypertension, etc.), neurodegenerative diseases (Spino-cerebral ataxia type 7, Spino-cerebral ataxia type 8, Spinal muscular atrophy, Opitz-Kaveggia syndrome, etc.) cancers (cervix, breast, lung cancer, etc.), and infectious diseases (viral) studied so far. This article encompasses discovery, biogenesis, classification, and evolutionary prospects of the existence of this junk rna along with the integrated networks involving chromatin remodelling, dosage compensation, genome imprinting, splicing regulation, post-translational regulation and proteomics. In conclusion, all the major human diseases are discussed with a facilitated technology transfer, advancements, loopholes, and tentative future research prospects have also been proposed.

关键词： Non‐ coding rna lncrna mirna Cancer Genetic diseases Neurodegenerative and cardiovascular diseases

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Knockdown of long non-coding rna small nucleolar rna host gene 9 or hexokinase 2 both suppress endometrial cancer cell proliferation and glycolysis

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JOUrnaL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 2021年第6期47卷 2196-2203页

作者： Wang, Lianhua Huang, Qiming Lin, Qingqing Chen, Lvxuan Shi, Qiyang Fujian Med Univ Dept Gynecol Affiliated Hosp 2 950 Donghai St Quanzhou Fujian Peoples R China Fujian Med Univ Dept Imaging Affiliated Hosp 2 Quanzhou Peoples R China Fujian Med Univ Dept Gynecol & Obstet Affiliated Hosp 2 Quanzhou Peoples R China

Aim Endometrial cancer (EC) is a common type of malignant gynecological cancer. Small nucleolar rna host gene 9 (SNHG9) has been discovered to serve a role in several types of cancer;however, the role of SNHG9 in EC remains unclear. The present study aimed to investigate the effects of lncrna SNHG9 on cell proliferation and glycolysis in EC cells. Methods SNHG9 and hexokinase 2 (HK2) mrna expression levels were measured by reverse transcription-quantitative PCR. Glucose consumption and lactate production were detected by the glycolysis cell-based assay kit. Cell Counting Kit-8 and colony formation assays were conducted to detect cell proliferation. The knockdown experiments of SNHG9 and HK2 were carried out by transfection of corresponding small interference rnas (sirna). The SNHG9-overexpressed plasmid was transfected into the cells to upregulate SNHG9. HK2 protein levels were analyzed by western blotting assay. Results SNHG9 expression levels were significantly upregulated in EC tissues and cells. The knockdown of SNHG9 subsequently effectively attenuated cell proliferation and glycolysis in vitro, while SNHG9 overexpression reported the opposite effects. Notably, the transfection of 2-DG partially reversed the promoting effect of SNHG9 on glycolysis. Downregulation of HK2 markedly decreased cell proliferation and glycolysis in EC cells antagonized SNHG9. Conclusion Either downregulation of SNHG9 or HK2 inhibits EC cell proliferation and glycolysis via repressing EC cell proliferation and glycolysis.

关键词： endometrial cancer glycolysis hexokinase 2 long non‐ coding rna small nucleolar rna host gene 9

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Long non-coding rna 01126 promotes periodontitis pathogenesis of human periodontal ligament cells via miR-518a-5p/HIF-1α/MAPK pathway

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CELL PROLIFERATION 2021年第1期54卷 e12957页

作者： Zhou, Mi Hu, Hui Han, Yineng Li, Jie Zhang, Yang Tang, Song Yuan, Yu Zhang, Xiaonan Chongqing Med Univ Coll Stomatol 426 Songshibei Rd Chongqing Peoples R China Chongqing Key Lab Oral Dis & Biomed Sci Chongqing Peoples R China Chongqing Municipal Key Lab Oral Biomed Engn Hige Chongqing Peoples R China Peking Univ Sch & Hosp Stomatol Dept Oral & Maxillofacial Surg Beijing Peoples R China

Background Periodontitis is a prevalent oral inflammatory disease, which can cause periodontal ligament to a local hypoxia environment. However, the mechanism of hypoxia associated long non-coding rnas (lncrnas) involved in periodontitis is still largely unknown. Methods Microarray was performed to detect the expression patterns of lncrnas in 3 pairs of gingival tissues from patients with periodontitis and healthy controls. The expression of lncrna 01126 (LINC01126), miR-518a-5p and hypoxia-inducible factor-1 alpha (HIF-1 alpha) in periodontal tissues and in human periodontal ligament cells (hPDLCs) under hypoxia was measured by quantitative real-time polymerase chain reaction or western blot. Fluorescence in situ hybridization and cell fraction assay were performed to determine the subcellular localization of LINC01126 and miR-518a-5p. Overexpression or knockdown of LINC01126 or HIF-1 alpha was used to confirm their biological roles in hPDLCs. MTT assays were performed to evaluate hPDLCs proliferation ability. Flow cytometry was used to detect apoptosis. ELISA was used to measure the expression levels of interleukin (IL)-1 beta, IL-6, IL-8 and TNF-alpha. Dual-luciferase reporter assays were performed to assess the binding of miR-518a-5p to LINC01126 and HIF-1 alpha. rna immunoprecipitation assay was used to identify whether LINC01126 and miR-518a-5p were significantly enriched in AGO-containing micro-ribonucleoprotein complexes. Results We selected LINC01126, which was the most highly expressed lncrna, to further verify its functions in periodontitis-induced hypoxia. The expression of LINC01126 was increased in periodontal tissues. In vitro experiment demonstrated that LINC01126 suppressed proliferation, promoted apoptosis and inflammation of hPDLCs under hypoxia via sponging miR-518a-5p. Moreover, we identified HIF-1 alpha acted as a direct target of miR-518a-5p in hPDLCs and LINC01126 promoted periodontitis pathogenesis by regulating the miR-518a-5p/HIF-1 alpha/M

关键词： HIF‐ 1α hypoxia long non‐ coding rna miR‐ 518a‐ 5p periodontitis

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Long non-coding rna ADAMTS9-AS1 inhibits the progression of prostate cancer by modulating the miR-142-5p/CCND1 axis

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JOUrnaL OF GENE MEDICINE 2021年第5期23卷 e3331页

作者： Zhou, Zhien Wu, Xingcheng Zhou, Yi Yan, Weigang Chinese Acad Med Sci Peking Union Med Coll Hosp Dept Urol 1 Shuaifuyuan Rd Beijing 100730 Peoples R China

Background Emerging evidence has implied the importance of long non-coding rnas in cancer development, including prostate cancer (PCa). Bioinformatic analyses have identified that ADAMTS9-AS1 may play a role in cancer progression. Methods A quantitative real-time polymerase chain reaction was conducted to measure ADAMTS9-AS1 expression level at messenger rna level. In vitro functional analyses were performed to investigate cell behaviors status under different conditions. Moreover, rescue assays were conducted to explore the potential mechanisms of ADAMTS9-AS1 in PCa progression. Results ADAMTS9-AS1 expression is down-regulated in PCa. Forcing ADAMTS9-AS1 expression impedes PCa cell proliferation via initiating cell apoptosis. Importantly, microrna-142-5p (miR-142-5p) mimic and small-interfering rna targeting cyclin D1 (CCND1, si-CCND1) could attenuate the inhibitory effects of ADAMTS9-AS1 overexpression on PCa cell growth. Conclusions Collectively, our results indicate that ADAMTS9-AS1 suppresses PCa progression by regulating the miR-142-5p/CCND1 axis, which provides a new mechanism for the progression of PCa.

关键词： ADAMTS9‐ AS1 CCND1 long non‐ coding rna miR‐ 142‐ 5p prostate cancer

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Profiling of specific long non-coding rna signatures identifies ST8SIA6-AS1 AS a novel target for breast cancer

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JOUrnaL OF GENE MEDICINE 2021年第2期23卷 e3286页

作者： Chen, Zhanghan Huang, Jie Feng, Yanling Li, Zehuan Jiang, Ying Fudan Univ Zhongshan Hosp Dept Gen Surg 180 Fenglin Rd Shanghai 200032 Peoples R China Fudan Univ Shanghai Publ Hlth Clin Ctr Dept Pathol Shanghai Peoples R China Fudan Univ Zhongshan Hosp Xiamen Branch Dept Gen Surg Fuzhou Fujian Peoples R China

Background Breast cancer is the most commonly diagnosed cancer among women and is also the leading cause of cancer death for which the treatment and methods of diagnosis remain unsatisfied. Long non-coding rna (lncrna) plays an important role in the occurrence and development of tumors, including breast cancer. We aimed to seek new and efficient treatment targets by analyzing the lncrna expression profiles of breast cancer. Methods A competitive endogenous rna microarray was used to investigate the profiles of differentially expressed lncrnas. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) validated the top differentially expressed lncrnas in 107 pairs of breast cancer tissues and adjacent normal tissues. cis- and trans-regulation mrnas of lncrnas were used to perform enrichment analysis. Cell function assays were used to explore the functions of ST8SIA6-AS1. Results Seven lncrnas, comprising ST8SIA6-AS1, lnc-HIST1H2BJ-5:1, lnc-PRICKLE2-3:2, RP1-86C11.7, RP11-15F12.1, ZNF670-ZNF695 and lnc-STRN3-12:1, were shown to be significantly up-regulated in breast cancer. lncrna ST8SIA6-AS1 was associated with TNM staging and Ki-67 index. The cell function assays showed that ST8SIA6-AS1 can promote the proliferation, migration and invasion of breast cancer cells. The functions of ST8SIA6-AS1 were explored and the competing endogenous rna mode showed that miR-4252 was a potential candidate. Its target genes were further predicted. The lncrna-protein mode showed three potential candidate rna binding proteins: NONO, QKI and RBMX. Conclusions lncrna ST8SIA6-AS1 can promote the proliferation, migration and invasion of breast cancer cells. By hypothesizing two different functional modes of ST8SIA6-AS1, we found lncrna ST8SIA6-AS1 may contribute to breast cancer progression through miR-4252 or interacting with rna binding proteins: NONO, QKI and RBMX.

关键词： biomarker breast cancer long non‐ coding rna ST8SIA6‐ AS1

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Functional interaction between long non-coding rna and microrna in rheumatoid arthritis

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JOUrnaL OF CLINICAL LABORATORY ANALYSIS 2020年第12期34卷 e23489页

作者： Liu, Weiwei Sheng, Li Nie, Lei Wen, Xiaoyun Mo, Xiaodan Northwest Minzu Univ Med Coll Lanzhou Peoples R China

Microrna (mirna) has received widespread attention for its role in several key cellular processes such as cell differentiation, cell proliferation, apoptosis, and autoimmune diseases. Although we now have a good understanding of mirna expression and function, our knowledge regarding the molecular mechanism of long non-coding rna (lncrna) is still in its infancy. In this review, we will briefly introduce the definition and function of lncrna and summarize the interactions between lncrna and mirna and their research progress in rheumatoid arthritis (RA). The expression of miR-16, miR-146a, miR-155, and miR-223 and the interactions between HOTAIR and miR138, ZFAS1 and miR-27a, and GAPLINC and miR-575 are representative examples that may augment the understanding of the pathogenesis of RA and help in the development of new biomarkers and target therapies.

关键词： long non‐ coding rna microrna rheumatoid arthritis

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Identification of Long Non-coding rna from inherent features using Machine Learning Techniques

Identification of Long Non-coding RNA from inherent features...

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International Conference on Bioinformatics and Systems Biology (BSB)

作者： Sreeshma, C. M. Manu, Madhavan Gopakumar, G. Natl Inst Technol Calicut Dept Comp Sci & Engn Kozhikode 673601 Kerala India

ISBN: (纸本)9781538664346

Long non-coding rnas are a distinctive class of non-coding rnas of length greater than 200 nucleotides and no protein coding potential. Lncrna plays an important role in genetic and epigenetic regulation. Major studies reveal that lncrnas are less conserved in their primary sequences and shows more functional characteristics at secondary structure level. The objective of this work is to identify an optimal sequencestructure combination for computational analysis of lncrnas. We also propose a novel secondary structure quantization which consider the existence of various structure elements. The feature combinations when used as input to classification of lncrnas from coding rnas, significant improvement in the results were obtained.

关键词： coding rna Non-coding rna Long noncoding rna (lncrna) rna Secondary structure rnafold Support Vector Machine Random Forest

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Non-coding rna in hepatocellular carcinoma: Mechanisms, biomarkers and therapeutic targets

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JOUrnaL OF HEPATOLOGY 2017年第3期67卷 603-618页

作者： Klingenberg, Marcel Matsuda, Akiko Diederichs, Sven Patel, Tushar German Canc Res Ctr Div RNA Biol & Canc Heidelberg Germany Univ Heidelberg Hosp Inst Pathol Heidelberg Germany Heidelberg Univ Hartmut Hoffmann Berling Int Grad Sch Mol & Cellu Heidelberg Germany Mayo Clin Dept Transplantat 4500 San Pablo Rd Jacksonville FL 32224 USA Mayo Clin Dept Canc Biol 4500 San Pablo Rd Jacksonville FL 32224 USA German Canc Consortium DKTK Freiburg Germany Univ Freiburg Div Canc Res Dept Thorac Surg Med Ctr Freiburg Germany Univ Freiburg Fac Med Freiburg Germany

The majority of the human genome is not translated into proteins but can be transcribed into rna. Even though the resulting non-coding rnas (ncrnas) do not encode for proteins, they contribute to diseases such as cancer. Here, we review examples of the functions of ncrnas in liver cancer and their potential use for the detection and treatment of liver cancer. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

关键词： Hepatocellular carcinoma HCC Long non coding rna lncrna microrna Liver cancer STAT3 Wnt Epithelial-to-mesenchymal transition Cancer stem cell

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