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LncReader: identification of dual functional long noncoding rnas using a multi -head self-attention mechanism

BRIEFINGS IN BIOINFORMATICS 2023年第1期24卷 bbac579-bbac579页

作者： Liu, Tianyuan Zou, Bohao He, Manman Hu, Yongfei Dou, Yiying Cui, Tianyu Tan, Puwen Li, Shaobin Rao, Shuan Huang, Yan Liu, Sixi Cai, Kaican Wang, Dong Southern Med Univ Guangzhou Peoples R China Univ Calif Davis Davis CA USA CAMS & Peking Union Med Coll Union NJ USA Southern Med Univ Nanfang Hosp Dept Thorac Surg Guangzhou Peoples R China Shenzhen Childrens Hosp Dept Hematol & Oncol Shenzhen Peoples R China Southern Med Univ Dept Bioinformat Guangzhou Peoples R China

Long noncoding ribonucleic acids (rnas;Lncrnas) endowed with both protein -coding and noncoding functions are referred to as 'dual functional lncrnas'. Recently, dual functional lncrnas have been intensively studied and identified as involved in various fundamental cellular processes. However, apart from time-consuming and cell -type -specific experiments, there is virtually no in silico method for predicting the identity of dual functional lncrnas. Here, we developed a deep -learning model with a multi -head self-attention mechanism, LncReader, to identify dual functional lncrnas. Our data demonstrated that LncReader showed multiple advantages compared to various classical machine learning methods using benchmark datasets from our previously reported cncrnadb project. Moreover, to obtain independent in-house datasets for robust testing, mass spectrometry proteomics combined with rna-seq and Ribo-seq were applied in four leukaemia cell lines, which further confirmed that LncReader achieved the best performance compared to other tools. Therefore, LncReader provides an accurate and practical tool that enables fast dual functional lncrna identification.

关键词： noncoding rna system biology deep learning

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Recent Insights into noncoding rnas in Primary Ovarian Insufficiency: Focus on Mechanisms and Treatments

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JOUrnaL OF CLINICAL ENDOCRINOLOGY & METABOLISM 2023年第8期108卷 1898-1908页

作者： Zhang, Jun-Hui Chen, Jia-Hua Guo, Bao Fang, Yuan Xu, Zu-Ying Zhan, Lei Cao, Yun-Xia Anhui Med Univ Dept Obstet & Gynecol Affiliated Hosp 1 Hefei 230022 Anhui Peoples R China Anhui Med Univ NHC Key Lab Study Abnormal Gametes & Reprod Tract Hefei 230032 Anhui Peoples R China Anhui Med Univ Key Lab Populat Hlth Life Cycle Minist Educ Peoples Republ China Hefei 230032 Anhui Peoples R China Anhui Prov Key Lab Reprod Hlth & Genet Hefei 230032 Anhui Peoples R China Anhui Prov Engn Res Ctr Biopreservat & Artificial Hefei 230032 Anhui Peoples R China Anhui Prov Inst Translat Med Hefei 230032 Anhui Peoples R China Anhui Med Univ Dept Obstet & Gynecol Affiliated Hosp 2 Hefei 230601 Anhui Peoples R China Anhui Med Univ Dept Obstet & Gynecol Affiliated Hosp 1 218 Jixi Rd Hefei 230022 Anhui Peoples R China Anhui Med Univ Dept Obstet & Gynecol Affiliated Hosp 2 678 Furong Rd Hefei 230601 Anhui Peoples R China

Context Primary ovarian insufficiency (POI) is a heterogeneous disease with an unknown underlying trigger or root cause. Recently many studies evaluated noncoding rnas (ncrnas), especially micrornas (mirnas), long noncoding rna (lncrnas), circular rnas (circrnas), and small interfering rnas (sirnas) for their associations with POI. Evidence acquisition In this review, we outline the biogenesis of various ncrnas relevant to POI and summarize the evidence for their roles in the regulation of disease occurrence and progression. Articles from 2003 to 2022 were selected for relevance, validity, and quality from results obtained in PubMed and Google Scholar using the following search terms: noncoding rnas;primary ovarian insufficiency;premature ovarian failure;noncoding rnas and primary ovarian insufficiency/premature ovarian failure;mirnas and primary ovarian insufficiency/premature ovarian failure;lncrnas and primary ovarian insufficiency/premature ovarian failure;sirnas and primary ovarian insufficiency/premature ovarian failure;circrnas and primary ovarian insufficiency/premature ovarian failure;pathophysiology;and potential treatment. All articles were independently screened for eligibility by the authors. Evidence synthesis This review summarizes the biological functions and synthesis of mirnas, lncrnas, sirnas, and circrnas in POI and discusses the findings of clinical and in vitro and in vivo studies. Although there is variability in the findings of individual studies, overall the available literature justifies the conclusion that dysregulated ncrnas play significant roles in POI. Conclusion The potential of ncrnas in the treatment of POI requires further investigation, as ncrnas derived from mesenchymal stem cell-secreted exosomes play pivotal roles and have considerable therapeutic potential in a multitude of diseases.

关键词： primary ovarian insufficiency premature ovarian failure noncoding rna mechanisms treatments

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Novel insights regarding the role of noncoding rnas in diabetes

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World Journal of Diabetes 2023年第7期14卷 958-976页

作者： Mirjana T Macvanin Zoran Gluvic Vladan Bajic Esma R Isenovic Department of Radiobiology and Molecular Genetics Vinča Institute of Nuclear Sciences-National Institute of the Republic of SerbiaUniversity of BelgradeBelgrade 11000Serbia Department of Endocrinology and Diabetes Clinic for Internal MedicineZemun Clinical HospitalSchool of MedicineUniversity of BelgradeBelgrade 11000Serbia

Diabetes mellitus(DM)is a group of metabolic disorders defined by hyperglycemia induced by insulin resistance,inadequate insulin secretion,or excessive glucagon *** 2021,the global prevalence of diabetes is anticipated to be 10.7%(537 million people).noncoding rnas(ncrnas)appear to have an important role in the initiation and progression of DM,according to a growing body of *** two major groups of ncrnas implicated in diabetic disorders are mirnas and long noncoding *** are singlestranded,short(17–25 nucleotides),ncrnas that influence gene expression at the post-transcriptional *** DM has reached epidemic proportions worldwide,it appears that novel diagnostic and therapeutic strategies are required to identify and treat complications associated with these diseases *** are gaining attention as biomarkers for DM diagnosis and potential treatment due to their function in maintaining physiological homeostasis via gene expression *** this review,we address the issue of the gradually expanding global prevalence of DM by presenting a complete and upto-date synopsis of various regulatory mirnas involved in these *** hope this review will spark discussion about ncrnas as prognostic biomarkers and therapeutic tools for *** examine and synthesize recent research that used novel,high-throughput technologies to uncover ncrnas involved in DM,necessitating a systematic approach to examining and summarizing their roles and possible diagnostic and therapeutic uses.

关键词： noncoding rna mirna Diabetes Circulating mirna biomarkers Therapeutic target CRISPR/Cas9 system

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Role of autophagy and its regulation by noncoding rnas in ovarian cancer

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EXPERIMENTAL BIOLOGY AND MEDICINE 2023年第12期248卷 1001-1012页

作者： Feng, Cong Yuan, Xingxing Heilongjiang Univ Chinese Med Affiliated Hosp 1 Dept Obstet & Gynecol Harbin 150040 Peoples R China Heilongjiang Univ Chinese Med Harbin 150040 Peoples R China Heilongjiang Acad Tradit Chinese Med Dept Gastroenterol Harbin 150001 Peoples R China

Autophagy is a self-digestion process by which misfolded proteins and damaged organelles in eukaryotic cells are degraded to maintain cellular homeostasis. This process is involved in the tumorigenesis, metastasis, and chemoresistance of various tumors such as ovarian cancer (OC). noncoding rnas (ncrnas), mainly including micrornas, long noncoding rnas, and circular rnas, have been extensively investigated in cancer research for their roles in the regulation of autophagy. Recent studies have shown that in OC cells, ncrnas can modulate the formation of autophagosomes, which affect tumor progression and chemoresistance. An understanding of the role of autophagy in OC progression, treatment, and prognosis is important, and the identification of the regulatory roles of ncrnas in autophagy leads to intervention strategies for OC therapy. This review summarizes the role of autophagy in OC and discusses the role of ncrna-mediated autophagy in OC, as an understanding of these roles may contribute to the development of potential therapeutic strategies for this disease.

关键词： Ovarian cancer autophagy noncoding rna tumorigenesis progression chemoresistance

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Role of noncoding rnas in pancreatic ductal adenocarcinoma associated cachexia

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AMERICAN JOUrnaL OF PHYSIOLOGY-CELL PHYSIOLOGY 2022年第6期323卷 C1624-C1632页

作者： Uddin, Md. Hafiz Mohammad, Ramzi M. Philip, Philip A. Azmi, Asfar S. Muqbil, Irfana Wayne State Univ Karmanos Canc Inst Sch Med Dept Oncol Detroit MI USA Henry Ford Hlth Syst Detroit MI USA Lawrence Tech Univ Dept Nat Sci Southfield MI USA

Cachexia is an acute syndrome that is very commonly observed in patients with cancer. Cachexia is the number one cause of death in patients with metastatic disease and is also the major factor for physical toxicity and financial burden. More importantly, the majority of patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) cancer undergo cachexia. Pancreatic cancer causes deaths of similar to 50,000 Americans and about 400,000 people worldwide every year. The high mortality rates in metastatic PDAC are due to systemic pathologies and cachexia, which quickens death in these patients. About 90% of all patients with PDAC undergo wasting of muscle causing mobility loss and leading to a number of additional pathological conditions. PDAC-associated cancer cachexia emanates from complex signaling cues involving both mechanical and biological signals. Tumor invasion is associated with the loss of pancreatic function-induced digestive disorders and malabsorption, which causes subsequent weight loss and eventually promotes cachexia. Besides, systemic inflammation of patients with PDAC could release chemical cues (e.g., cytokine-mediated Atrogin-1/MAFbx expression) that participate in muscle wasting. Our understanding of genes, proteins, and cytokines involved in promoting cancer cachexia has evolved considerably. However, the role of epigenetic factors, particularly the role of noncoding rnas (ncrnas) in regulating PDAC-associated cachexia is less studied. In this review article, the most updated knowledge on the various ncrnas including micrornas (miRs), long noncoding rna (lncrnas), piwi interacting rnas (Piwirnas), small nucleolar rna (snornas), and circular rnas (circrna) and their roles in cancer cachexia are described.

关键词： cachexia muscle wasting noncoding rna pancreatic cancer tissue biopsy

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Emerging function and clinical significance of extracellular vesicle noncoding rnas in lung cancer

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MOLECULAR THERAPY-ONCOLYTICS 2022年 24卷 814-833页

作者： Shan, Chan Liang, Yan Cai, Hongjing Wang, Fei Chen, Xinzhe Yin, Qikun Wang, Kun Wang, Yin Qingdao Univ Coll Med Affiliated Hosp Inst Translat Med Qingdao 266021 Peoples R China Qingdao Univ Sch Pharm Dept Pharmaceut Qingdao 266021 Peoples R China Yantai Univ Sch Pharm Key Lab Mol Pharmacol & Drug Evaluat Yantai 264005 Peoples R China

Lung cancer (LC) is a commonly diagnosed cancer with an unsatisfactory prognosis. Extracellular vesicles (EVs) are lipid bilayer-delimited particles that mediate cell-cell communication by transporting various biomacromolecules, such as nucleic acids, proteins, and lipids. noncoding rnas (ncrnas),including micrornas, circular rnas, and long noncoding rnas, are important noncoding transcripts that play critical roles in a variety of physiological and pathological processes,especially in cancer. ncrnas have been verified to be packaged into EVs and transported between LC cells and stromal cells, regulating multiple LC malignant phenotypes, such as proliferation, migration, invasion, epithelial-mesenchymal transition, metastasis, and treatment resistance. Additionally,EVs can be detected in various body fluids and are associated with the stage, grade, and metastasis of LC. Herein, we summarize the biological characteristics and functions of EV ncrnas in the biological processes of LC, focusing on their potential to serve as diagnostic and prognostic biomarkers of LC as well as their probable role in the clinical treatment of LC. EV ncrnas provide a new perspective for understanding the mechanism underlying LC pathogenesis and development,which might benefit numerous LC patients in the future.

关键词： extracellular vesicle noncoding rna lung cancer progression prospective biomarkers clinical values

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CANCER MANAGEMENT AND RESEARCH 2022年 14卷 2215-2224页

作者： Lu, Ling Liang, Qiaoyan Zhang, Xinyi Xu, Yumeng Meng, Dehua Liang, Zhaofeng Jiangsu Univ Affiliated Hosp 4 Child Healthcare Dept Zhenjiang Peoples R China Peoples Liberat Army Navy No 971 Hosp Hlth Care Dept Qingdao Peoples R China Jiangsu Univ Sch Med Zhenjiang Peoples R China Dongtai Peoples Hosp Dept Allergy Yancheng Peoples R China Jiangsu Univ Sch Med Email 301 Xuefu Rd Zhenjiang 212013 Jiangsu Peoples R China Dongtai Peoples Hosp Dept Allergy 02 Fukang West Rd Yancheng 224200 Jiangsu Peoples R China

Gastric cancer (GC) is one of the most common malignant cancers that seriously affect human health. Autophagy is a highly conserved self-defense mechanism found to plays an important role in the occurrence, progression, drug resistance, and prognosis of GC. noncoding rnas (ncrnas) play a critical role in the occurrence and development of a variety of diseases including GC. In recent years, increasing attention has been given to research on autophagy-related ncrnas, such as mirna, lncrna, and circrna in GC. Herein, we briefly summarize the roles, functions, and the research progress of autophagy and autophagy-related ncrnas in GC with a focus on the potential application in GC tumorigenesis, development, prognosis, and drug resistance. We also discussed prospects of clinical application, future research direction, and challenges in future research of autophagy-related ncrnas.

关键词： gastric cancer autophagy noncoding rna function

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Regulatory effects of noncoding rnas on the interplay of oxidative stress and autophagy in cancer malignancy and therapy

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SEMINARS IN CANCER BIOLOGY 2022年第0期83卷 269-282页

作者： Liu, Pei-Feng Farooqi, Ammad Ahmad Peng, Sheng-Yao Yu, Tzu-Jung Dahms, Hans-Uwe Lee, Cheng-Hsin Tang, Jen-Yang Wang, Sheng-Chieh Shu, Chih-Wen Chang, Hsueh-Wei Kaohsiung Med Univ Coll Life Sci Dept Biomed Sci & Environm Biol PhD Program Life Sci Kaohsiung Taiwan Kaohsiung Med Univ Hosp Dept Med Res Kaohsiung Taiwan Kaohsiung Med Univ Ctr Canc Res Kaohsiung Taiwan Natl Sun Yat Sen Univ Inst Biomed Sci Kaohsiung Taiwan Inst Biomed & Genet Engn IBGE Dept Mol Oncol Islamabad Pakistan Kaohsiung Med Univ Grad Inst Nat Prod Kaohsiung Taiwan Kaohsiung Med Univ Res Ctr Environm Med Kaohsiung Taiwan Natl Sun Yat Sen Univ Dept Marine Biotechnol & Resources Kaohsiung 80424 Taiwan Kaohsiung Med Univ Coll Med Fac Med Dept Radiat Oncol Kaohsiung Taiwan Kaohsiung Med Univ Hosp Dept Radiat Oncol Kaohsiung Taiwan Natl Sun Yat Sen Univ Inst Biopharmaceut Sci Kaohsiung Taiwan Kaohsiung Med Univ Hosp Canc Ctr Kaohsiung Taiwan Kaohsiung Med Univ Dept Biomed Sci & Environm Biol Kaohsiung Taiwan

ABSTR A C T noncoding rnas (ncrnas) regulation of various diseases including cancer has been extensively studied. Reactive oxidative species (ROS) elevated by oxidative stress are associated with cancer progression and drug resistance, while autophagy serves as an ROS scavenger in cancer cells. However, the regulatory effects of ncrnas on autophagy and ROS in various cancer cells remains complex. Here, we explore how currently investigated ncrnas, mainly mirnas and lncrnas, are involved in ROS production through modulating antioxidant genes. The regulatory effects of mirnas and lncrnas on autophagy-related (ATG) proteins to control autophagy ac-tivity in cancer cells are discussed. Moreover, differential expression of ncrnas in tumor and normal tissues of cancer patients are further analyzed using The Cancer Genome Atlas (TCGA) database. This review hypothesizes links between ATG genes-or antioxidant genes-modulated ncrnas and ROS production, which might result in tumorigenesis, malignancy, and cancer recurrence. A better understanding of the regulation of ROS and auto-phagy by ncrnas might advance the use of ncrnas as diagnostic and prognostic markers as well as therapeutic targets in cancer therapy.

关键词： noncoding rna Oxidative stress Autophagy Cancer Diagnostic marker Therapeutic marker

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The role and mechanism of noncoding rnas in regulation of metabolic reprogramming in hepatocellular carcinoma

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INTErnaTIONAL JOUrnaL OF CANCER 2022年第3期151卷 337-347页

作者： Liao, Wenwei Du, Jinpeng Wang, Zhen Feng, Qingbo Liao, Mingheng Liu, Huixian Yuan, Kefei Zeng, Yong Sichuan Univ West China Hosp State Key Lab Biotherapy Dept Liver Surg & Liver Transplantat Chengdu Peoples R China Sichuan Univ West China Hosp Ctr Canc Chengdu Peoples R China Collaborat Innovat Ctr Biotherapy Chengdu Peoples R China Sun Yat Sen Univ Affiliated Hosp 1 Dept Postanesthesia Care Unit Guangzhou Peoples R China Sun Yat Sen Univ Affiliated Hosp 1 Surg Anesthesia Ctr Guangzhou Peoples R China

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Metabolic reprogramming is considered to be an important hallmark of cancer. Emerging studies have demonstrated that noncoding rnas (ncrnas) are closely associated with metabolic reprogramming of HCC. Ncrnas can directly regulate the expressions or functions of metabolic enzymes or indirectly regulate the metabolism of HCC cells through some vital signaling pathways. Until now, the mechanisms of HCC development and progression remain largely unclear, and understanding the regulatory mechanism of ncrnas on metabolic reprogramming of HCC may provide an important basis for breakthrough progress in the treatment of HCC. In this review, we summarize the ncrnas involved in regulating metabolic reprogramming of HCC. Specifically, the regulatory roles of ncrnas in glucose, lipid and amino acid metabolism are elaborated. In addition, we discuss the molecular mechanism of ncrnas in regulation of metabolic reprogramming and possible therapeutic strategies that target the metabolism of cancer cells by modulating the expressions of specific ncrnas.

关键词： circrna hepatocellular carcinoma lncrna metabolic reprogramming noncoding rna

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noncoding rnas as Promising Diagnostic Biomarkers and Therapeutic Targets in Intestinal Fibrosis of Crohn's Disease: The Path From Bench to Bedside

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INFLAMMATORY BOWEL DISEASES 2021年第7期27卷 971-982页

作者： Zhou, Long-Yuan Lin, Si-Nan Rieder, Florian Chen, Min-Hu Zhang, Sheng-Hong Mao, Ren Sun Yat Sen Univ Affiliated Hosp 1 Dept Gastroenterol 58 Zhongshan Rd 2nd Guangzhou 510080 Peoples R China Cleveland Clin Digest Dis & Surg Inst Dept Gastroenterol Hepatol & Nutr Cleveland OH 44106 USA

Fibrosis is a major pathway to organ injury and failure, accounting for more than one-third of deaths worldwide. Intestinal fibrosis causes irreversible and serious clinical complications, such as strictures and obstruction, secondary to a complex pathogenesis. Under the stimulation of profibrotic soluble factors, excessive activation of mesenchymal cells causes extracellular matrix deposition via canonical transforming growth factor-beta/Smads signaling or other pathways (eg, epithelial-to-mesenchymal transition and endothelial-to-mesenchymal transition) in intestinal fibrogenesis. In recent studies, the importance of noncoding rnas (ncrnas) stands out in fibrotic diseases in that ncrnas exhibit a remarkable variety of biological functions in modulating the aforementioned fibrogenic responses. In this review, we summarize the role of ncrnas, including the emerging long ncrnas and circular rnas, in intestinal fibrogenesis. Notably, the translational potential of ncrnas as diagnostic biomarkers and therapeutic targets in the management of intestinal fibrosis is discussed based on clinical trials from fibrotic diseases in other organs. The main points of this review include the following: Characteristics of ncrnas and mechanisms of intestinal fibrogenesis Wide participation of ncrnas (especially the emerging long ncrnas and circular rnas) in intestinal fibrosis, including transforming growth factor-beta signaling, epithelial-to-mesenchymal transition/endothelial-to-mesenchymal transition, and extracellular matrix remodeling Translational potential of ncrnas in the diagnosis and treatment of intestinal fibrosis based on clinical trials from fibrotic diseases in other organs

关键词： intestinal fibrosis Crohn's disease noncoding rna extracellular matrix

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