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microrna-370-5p inhibits pigmentation and cell proliferation by downregulating mitogen-activated protein kinase kinase kinase 8 expression in sheep melanocytes

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Journal of Integrative Agriculture 2023年第4期22卷 1131-1141页

作者： JI Kai-yuan WEN Ru-jun WANG Zheng-zhou TIAN Qian-qian ZHANG Wei ZHANG Yun-hai Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control College of Animal Science and TechnologyAnhui Agricultural UniversityHefei 230036P.R.China Anhui Province Key Laboratory of Local Livestock and Poultry Genetic Resources Conservation and Bio-Breeding College of Animal Science and TechnologyAnhui Agricultural UniversityHefei 230036P.R.China Linquan Comprehensive Experimental Station Anhui Agricultural UniversityLinquan 236400P.R.China

In mammals,micrornas(miRNAs)play key roles in multiple biological processes by regulating the expression of target genes.Studies have found that the levels of miR-370-5p expression differ significantly in the skins of sheep with different hair colors;however,its function remains unclear.In this study,we investigated the roles of miR-370-5p in sheep melanocytes and found that the overexpression of miR-370-5p significantly inhibited cell proliferation(P<0.01),tyrosinase activity(P=0.001)and significantly reduced(P<0.001)melanin production.Functional prediction revealed that the 3′-untranslated region(UTR)of MAP3K8 has a putative miR-370-5p binding site,and the interaction between these two molecules was confirmed using luciferase reporter assays.In situ hybridization assays revealed that MAP3K8 is expressed in the cytoplasm of melanocytes.The results of quantitative RT-PCR and Western blotting analyses revealed that overexpression of miR-370-5p in melanocytes significantly inhibits(P<0.01)MAP3K8 expression via direct targeting of its 3′UTR.Inhibition of MAP3K8 expression by siRNA-MAP3K8 transfection induced a significant inhibition(P<0.01)of melanocyte proliferation and significant reduction(P<0.001)in melanin production,which is consistent with our observations for miR-370-5p.Target gene rescue experiments indicated that the expression of MAP3K8 in melanocytes co-transfected with miR-370-5p and MAP3K8-cDNA(containing sites for the targeted binding to miR-370-5p)was significantly rescued(P≤0.001),which subsequently promoted significant increases in cell proliferation(P<0.001)and melanin production(P<0.01).Collectively,these findings indicate that miR-370-5p plays a functional role in inhibiting sheep melanocyte proliferation and melanogenesis by downregulating the expression of MAP3K8.

关键词： microrna mitogen-activated protein kinase kinase kinase 8 melanogenesis sheep melanocytes cell proliferation

primiReference: a reference for analysis of primary-microrna expression in single-nucleus sequencing data

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Journal of Genetics and Genomics 2023年第2期50卷 108-121页

作者： Amy E.Elias Thomas A.Nuñez Bianca Kun Jill A.Kreiling Roche WilmingtonMA 01887USA. Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRI02903USA Public Health Genetics University of PittsburghPittsburghPA 15260USA

Single-nucleus RNA-sequencing technology has revolutionized understanding of nuanced changes in gene expression between cell types within tissues.Unfortunately,our understanding of regulatory RNAs,such as micrornas(miRNAs),is limited through both single-cell and single-nucleus techniques due to the short length of miRNAs in the cytoplasm and the incomplete reference of longer primary miRNA(pri-miRNA)transcripts in the nucleus.We build a custom reference to align and count pri-miRNA sequences in singlenucleus data.Using young and aged subventricular zone(SVZ)nuclei,we show differential expression of pri-miRNAs targeting genes involved in neural stem cells(NSC)differentiation in the aged SVZ.Furthermore,using wild-type and 5XFAD mouse model cortex nuclei,to validate the use of primiReference,we find cell-type-specific expression of pri-miRNAs known to be involved in Alzheimer’s disease(AD).pri-miRNAs likely contribute to NSC dysregulation with age and AD pathology.primiReference is paramount in capturing a global profile of gene expression and regulation in single-nucleus data and can provide key insights into cell-type-specific expression of pri-miRNAs,paving the way for future studies of regulation and pathway dysregulation.By looking at pri-miRNA abundance and transcriptional differences,regulation of gene expression by miRNAs in disease and aging can be further explored.

关键词： Primary-microrna Aging Subventricular zone Alzheimer’s disease Single-nucleus RNA-Seq microrna Transcriptomics

Altered microrna expression profiles of human spermatozoa in normal fertile men of different ages

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Asian Journal of Andrology 2023年第6期25卷 737-744页

作者： Ming-Jia Zhao Yao-Nan Zhang Yong-Ping Zhao Xian-Bing Chen Bao-Sheng Han Ning Ding Yi-Qun Gu Shu-Song Wang Jing Ma Mei-Ling Liu Graduate School of Peking Union Medical College Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China National Health Commission Key Laboratory of Male Reproductive Health National Research Institute for Family PlanningBeijing 100081China Department of Reproduction and Genetics Maternity and Child Health Care HospitalTangshan 063000China Department of Family Planning and Reproductive Medicine Peking University People’s HospitalBeijing 100081China Hebei Key Laboratory of Reproductive Medicine Hebei Institute of Reproductive Health Science and TechnologyShijiazhuang 050071China

micrornas(miRNAs)are mediators of the aging process.The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility.Twenty-seven donors were divided into three groups by age(Group A,n=8,age:20–30 years;Group B,n=10,age:31–40 years;and Group C,n=9,age:41–55 years)for high-throughput sequencing analysis.Samples from 65 individuals(22,22,and 21 in Groups A,B,and C,respectively)were used for validation by quantitative real-time polymerase chain reaction(qRT-PCR).A total of 2160 miRNAs were detected:1223 were known,937 were newly discovered and unnamed,of which 191 were expressed in all donors.A total of 7,5,and 17 differentially expressed micrornas(DEMs)were found in Group A vs B,Group B vs C,and Group A vs C comparisons,respectively.Twenty-two miRNAs were statistically correlated with age.Twelve miRNAs were identified as age-associated miRNAs,including hsa-miR-127-3p,mmu-miR-5100_L+2R-1,efu-miR-9226_L-2_1ss22GA,cgr-miR-1260_L+1,hsa-miR-652-3p_R+1,pal-miR-9993a-3p_L+2R-1,hsa-miR-7977_1ss6AG,hsa-miR-106b-3p_R-1,hsa-miR-186-5p,PC-3p-59611_111,hsa-miR-93-3p_R+1,and aeca-mir-8986ap5_1ss1GA.There were 9165 target genes of age-associated miRNAs.Gene Ontology(GO)analysis of the target genes identified revealed enrichment of protein binding,membrane,cell cycle,and so on.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways,such as signaling pathways regulating stem cell pluripotency,metabolic pathways,and the Hippo signaling pathway.This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.

关键词： age fertility microrna spermatozoa

Stage-specific treatment of colorectal cancer: A microrna-nanocomposite approach

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Journal of Pharmaceutical Analysis 2023年第11期13卷 1235-1251页

作者： Adewale Oluwaseun Fadaka Taiwo Akinsoji Ashwil Klein Abram Madimabe Madiehe Mervin Meyer Marshall Keyster Lucky Mashudu Sikhwivhilu Nicole Remaliah Samantha Sibuyi Department of Anesthesia Division of Pain ManagementCincinnati Children's Hospital Medical CenterCincinnatiOH45229USA Department of Science and Innovation/Mintek Nanotechnology Innovation Centre Biolabels NodeDepartment of BiotechnologyFaculty of Natural SciencesUniversity of the Western CapeBellville7535South Africa School of Medicine Southern Illinois UniversitySpringfieldIL62702USA Plant Omics Laboratory Department of BiotechnologyFaculty of Natural SciencesUniversity of the Western CapeBellville7535South Africa Nanobiotechnology Research Group Department of BiotechnologyFaculty of Natural SciencesUniversity of the Western CapeBellville7535South Africa Environmental Biotechnology Laboratory Department of BiotechnologyFaculty of Natural SciencesUniversity of the Western CapeBellville7535South Africa Department of Science and Innovation/Mintek Nanotechnology Innovation Centre Advanced Materials DivisionMintekJohannesburg2125South Africa h Department of ChemistryFaculty of ScienceEngineering and AgricultureUniversity of VendaThohoyandou0950South Africa

Colorectal cancer(CRC)is among the leading causes of cancer mortality.The lifetime risk of developing CRC is about 5%in adult males and females.CRC is usually diagnosed at an advanced stage,and at this point therapy has a limited impact on cure rates and long-term survival.Novel and/or improved CRC therapeutic options are needed.The involvement of micrornas(miRNAs)in cancer development has been reported,and their regulation in many oncogenic pathways suggests their potent tumor suppressor action.Although miRNAs provide a promising therapeutic approach for cancer,challenges such as biodegradation,specificity,stability and toxicity,impede their progression into clinical trials.Nanotechnology strategies offer diverse advantages for the use of miRNAs for CRC-targeted delivery and therapy.The merits of using nanocarriers for targeted delivery of miRNA-formulations are presented herein to highlight the role they can play in miRNA-based CRC therapy by targeting different stages of the disease.

关键词： Colorectal cancer microrna Nanotechnology Nanocarriers OncomiRs TSmiRs

micrornas-微生物互作调控机体脂肪代谢研究进展

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中国科学：生命科学 2024年第2期54卷 300-307页

作者：胡竑贺芳邓志颖周锡红印遇龙湖南农业大学动物科学技术学院长沙410128 中国科学院亚热带农业生态研究所动物营养生理与代谢过程湖南省重点实验室长沙410125

微生物和micrornas均参与机体脂肪酸吸收、转运和从头合成,以及脂肪动员和储存等代谢过程的调节.宿主分泌的micrornas可通过调控微生物生长和代谢影响脂肪代谢.微生物一方面可影响宿主micrornas分泌,另一方面其自身也可直接分泌microRN... 详细信息

微生物和micrornas均参与机体脂肪酸吸收、转运和从头合成,以及脂肪动员和储存等代谢过程的调节.宿主分泌的micrornas可通过调控微生物生长和代谢影响脂肪代谢.微生物一方面可影响宿主micrornas分泌,另一方面其自身也可直接分泌micrornas,并调节宿主的代谢功能.本文综述了micrornas和微生物对机体脂肪代谢的影响和调控机制,重点探讨了micrornas和微生物互作调控脂肪代谢的研究进展和作用机制,以期为精准靶向预防或治疗脂肪代谢紊乱相关疾病提供新的思路和依据.

关键词：微生物 microrna 脂肪代谢胞外囊泡

microrna regulation and host interaction in response to Aspergillus exposure

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BIOCELL 2022年第2期46卷 339-356页

作者： MANSI SHRIVASTAVA DIKSHA PANDEY POONAM SHARMA RAMBIR SINGH Department of Biomedical Sciences Bundelkhand UniversityJhansi284128India Department of Zoology Indira Gandhi National Tribal UniversityAmarkantak484886India Department of Horticulture Aromatic and Medicinal PlantsMizoram UniversityAizawl796004India

Aspergillus is a group of conidial fungi,isolated from soil and litter,cause serious diseases in humans and animals.This ubiquitous fungus is prevalent in the air and inhalation of fungal spores is common.Fungal diseases from Aspergillus became a major health problem and are difficult to manage because they tend to be chronic and invasive,hard to diagnose and difficult to exterminate with antifungal drugs.Although,immune responses play vital roles in monitoring the fate of fungal infections and regulation of the immune responses against fungal infections might be an effective approach for controlling and reducing the pathological damages.Recent studies have shown that micrornas(miRNAs)are assembly of regulators which modulates the immune responses during fungal infections through diversified cellular mechanisms.These small non-coding RNA sequences regulate gene expression,mostly at the post-transcriptional level and have emerged as the controller of gene expression of at least 30%human genes.Therefore,miRNAs might be considered as one of the potential goals in immunotherapy for fungal infections.The objective of this review is to explore the role of miRNAs in host recognition processes and understanding the modulation of regulatory pathways in response to Aspergillus exposure.

关键词： Fungal exposure Aspergillus microrna Immune response

Regulatory RNAs,microrna,long-non coding RNA and circular RNA roles in colorectal cancer stem cells

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World Journal of Gastrointestinal Oncology 2022年第4期14卷 748-764页

作者： Hsiao-Mei Chao Teh-Wei Wang Edward Chern Shan-hui Hsu Department of Pathology Wan Fang HospitalTaipei Medical UniversityTaipei 11696Taiwan Department of Pathology School of MedicineCollege of MedicineTaipei Medical UniversityTaipei 110Taiwan niChe Lab for Stem Cell and Regenerative Medicine Department of Biochemical Science and TechnologyNational Taiwan UniversityTaipei 10617Taiwan Institute of Polymer Science and Engineering National Taiwan UniversityTaipei 10617Taiwan

The properties of cancer stem cells(CSCs),such as self-renewal,drug resistance,and metastasis,have been indicated to be responsible for the poor prognosis of patients with colon cancers.The epigenetic regulatory network plays a crucial role in CSC properties.Regulatory non-coding RNA(ncRNA),including micrornas,long noncoding RNAs,and circular RNAs,have an important influence on cell physiopathology.They modulate cells by regulating gene expression in different ways.This review discusses the basic characteristics and the physiological functions of colorectal cancer(CRC)stem cells.Elucidation of these ncRNAs will help us understand the pathological mechanism of CRC progression,and they could become a new target for cancer treatment.

关键词： Regulatory RNAs microrna Long-non coding RNA Circular RNA Colorectal cancer Cancer stem cell Stemness

Hepatitis B Virus Surface Antigen Promotes Stemness of Hepatocellular Carcinoma through Regulating microrna-203a

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Journal of Clinical and Translational Hepatology 2023年第1期11卷 118-129页

作者： Yu-Fei Qin Zi-Yu Zhou Hou-Wei Fu Hao-Ming Lin Lei-Bo Xu Wen-Rui Wu Chao Liu Xiao-Lin Xu Rui Zhang Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of BiliaryPancreatic Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdongChina Department of Ultrasound Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdongChina

Background and Aims:Patients with persistent positive hepatitis B surface antigen(HBsAg),even with a low HBVDNA load,have a higher risk of hepatocellular carcinoma(HCC)than those without HBV infection.Given that tumor stemness has a critical role in the occurrence and maintenance of neoplasms,this study aimed to explore whether HBsAg affects biological function and stemness of HCC by regulating microrna,and to explore underlying mechanisms.Methods:We screened out miR-203a,the most significant down-regulated microrna in the microarray analysis of HBsAg-positive samples and focused on that miRNA in the ensuing study.In vitro and in vivo functional experiments were performed to assess its regulatory function.The effect of miR-203a on stemness and the possible correlation with BMI1 were analyzed in this study.Results:MiR-203a was significantly down-regulated in HBsAg-positive HCC with the sharpest decrease shown in microarray analysis.The negative correlation between miR-203a and HBsAg expression was confirmed by quantitative real-time PCR after stimulation or overexpression/knockdown of HBsAg in cells.We demonstrated the function of miR-203a in inhibiting HCC cell proliferation,migration,clonogenic capacity,and tumor development in vivo.Furthermore,the overexpression of miR-203a remarkably increases the sensitivity of tumor cells to 5-FU treatment and decreases the proportion of HCC cells with stem markers.In concordance with our study,the survival analysis of both The Cancer Genome Atlas database and samples in our center indicated a worse prognosis in patients with low level of miR-203a.We also found that BMI1,a gene maintains the self-renewal capacity of stem cells,showed a significant negative correlation with miR-203a in HCC specimen(p<0.001).Similarly,opposite BMI1 changes after overexpression/knockdown of miR203a were also confirmed in vitro.Dual luciferase reporting assay suggested that miR-203a may regulate BMI1 expression by direct binding.Conclusions:HBsAg may promote the development of HCC and tumor stem

关键词： Hepatitis B surface antigen Hepatocellular carcinoma microrna Stemness

MiRNA-122在运动改善非酒精性脂肪肝中的作用

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中国组织工程研究 2024年第2期28卷 272-279页

作者：郭项英彭子富何亦敏房洪波姜宁天津体育学院天津市运动生理与运动医学重点实验室天津市301617

背景:近年来,随着人们生活水平的提高,非酒精性脂肪肝有逐渐增多的趋势。miRNA-122是肝脏中最丰富的miRNA之一,在维持肝脏内环境稳定和分化中起重要作用。运动训练是非酒精性脂肪肝的非药物治疗手段,运动可能通过调节肝脏miRNA-122的表... 详细信息

背景:近年来,随着人们生活水平的提高,非酒精性脂肪肝有逐渐增多的趋势。miRNA-122是肝脏中最丰富的miRNA之一,在维持肝脏内环境稳定和分化中起重要作用。运动训练是非酒精性脂肪肝的非药物治疗手段,运动可能通过调节肝脏miRNA-122的表达改善肝脏脂代谢等过程。目的:综述miRNA-122对非酒精性脂肪肝相关病理因素的影响,以及运动对miRNA-122表达和非酒精性脂肪肝发生发展的影响。方法:第一作者检索中国知网、万方数据库和维普数据库、PubMed、Geenmedical、EBSCO、Medline、Web of Science和Elsevier数据库,以“non-alcoholic fatty liver disease,microrna,microrna-122,lipid metabolism,inflammatory response,insulin resistance,exercise,physical exercise,exercise training”为英文检索词,以“非酒精性脂肪肝,microrna,microrna-122,脂代谢,炎症反应,胰岛素抵抗,运动,体育活动”为中文检索词,检索2022-06-05前发表的所有相关文献,并对其进行了筛选、归纳、分析、总结,最后纳入68篇文献进行综述。结果与结论:①与健康对照组相比,非酒精性脂肪肝患者循环miRNA-122表达升高,miRNA-122在非酒精性脂肪肝的不同阶段表现出不同的表达情况。②miRNA-122可通过靶向mRNA上的碱基互补配对位点或直接作为某些RNA受体的生理配体调控下游相关蛋白的表达,影响非酒精性脂肪肝脂代谢、炎症反应和胰岛素抵抗等致病因素。③不同的运动方式对非酒精性脂肪肝均有改善作用,对于非酒精性脂肪肝患者,每周需要完成至少120 min的中等强度运动才可产生积极作用;对于能够耐受各种运动的非酒精性脂肪肝患者,应优先考虑每周进行四五次有氧和抗阻运动结合的训练。运动强度应为最大心率的50%-70%,并持续>3个月;而对于耐受力较差的非酒精性脂肪肝患者,抗阻运动可能比有氧运动更可行;此外,非酒精性脂肪肝患者还可根据自身的疾病情况(如肝酶、脂质水平)选择运动方式。④运动可作为防治非酒精性脂肪肝、减轻肝脂肪变性、降低肝脏炎症反应和胰岛素抵抗的可行策略。⑤运动训练可调控机体miRNA-122的表达,但在非酒精性脂肪肝患者中,运动对miRNA-122及其相关信号通路的影响还有待研究。

关键词：非酒精性脂肪肝运动 miRNA-122 脂代谢炎症反应胰岛素抵抗 microrna