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

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

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Microrna miR-2765-3p regulates reproductive diapause by targeting FoxO in Galeruca daurica

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Insect Science 2023年第2期30卷 279-292页

作者： Tian-Feng Duan Ling Li Hai-Chao Wang Bao-Ping Pang Research Center for Grassland Entomology Inner Mongolia Agricultural UniversityHohhotChina

The forkhead box O(FoxO),as a conserved transcription factor,plays an indispensable role in regulating insect diapause.However,how FoxO is regulated to control diapause in insects remains unknown.In this study,we discovered functional binding sites for miR-2765-3p in the 3′untranslated region of FoxO in Galeruca daurica.The luciferase reporter assay showed that miR-2765-3p targeted FoxO and suppressed its expression.The expression profiles of miR-2765-3p and FoxO displayed opposite patterns during the female developmental process.Overexpression of miR-2765-3p by the injection of the miR-2765-3p agomir into adult females reduced FoxO expression,leading to the suppression of lipid accumulation,promotion of ovarian development,and inhibition of reproductive diapause.This is similar to the phenotype that results from the depletion of FoxO by injecting dsFoxO into adult females.In addition,the repression of miR-2765-3p by injecting the miR-2765-3p antagomir increased the FoxO transcript level,leading to the stimulation of lipid accumulation,depression of ovarian development,and induction of reproductive diapause.A hormone injection assay showed that the juvenile hormone(JH)agonist(methoprene)upregulated miR-2765-3p and downregulated FoxO.Notably,injecting methoprene rescued ovarian development defects associated with miR-2765-3p inhibition.These findings indicate that the JH/miR-2765-3p/FoxO axis plays a vital role in the regulation of reproductive diapause in G.daurica.

关键词： diapause FoxO Galeruca daurica juvenile hormone Microrna

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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

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Microrna biomarkers in frontotemporal dementia and to distinguish from Alzheimer's disease and amyotrophic lateral sclerosis

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Neural Regeneration Research 2022年第7期17卷 1412-1422页

作者： Bridget Martinez Philip V.Peplow Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

Frontotemporal lobar degeneration describes a group of progressive brain disorders that primarily are associated with atrophy of the prefrontal and anterior temporal lobes.Frontotemporal lobar degeneration is considered to be equivalent to frontotemporal dementia.Frontotemporal dementia is characterized by progressive impairments in behavior,executive function,and language.There are two main clinical subtypes:behavioral-variant frontotemporal dementia and primary progressive aphasia.The early diagnosis of frontotemporal dementia is critical for developing management strategies and interventions for these patients.Without validated biomarkers,the clinical diagnosis depends on recognizing all the core or necessary neuropsychiatric features,but misdiagnosis often occurs due to overlap with a range of neurologic and psychiatric disorders.In the studies reviewed a very large number of Micrornas were found to be dysregulated but with limited overlap between individual studies.Measurement of specific miRNAs singly or in combination,or as miRNA pairs(as a ratio)in blood plasma,serum,or cerebrospinal fluid enabled frontotemporal dementia to be discriminated from healthy controls,Alzheimer’s disease,and amyotrophic lateral sclerosis.Furthermore,upregulation of miR-223-3p and downregulation of miR-15a-5p,which occurred both in blood serum and cerebrospinal fluid,distinguished behavioral-variant frontotemporal dementia from healthy controls.Downregulation of miR-132-3p in frontal and temporal cortical tissue distinguished frontotemporal lobar degeneration and frontotemporal dementia,respectively,from healthy controls.Possible strong miRNA biofluid biomarker contenders for behavioral-variant frontotemporal dementia are miR-223-3p,miR-15a-5p,miR-22-3p in blood serum and cerebrospinal fluid,and miR-124 in cerebrospinal fluid.No miRNAs were identified able to distinguish between behavioral-variant frontotemporal dementia and primary progressive aphasia subtypes.Further studies are warranted on investigating miRNA expression in b

关键词： Alzheimer’s disease amyotrophic lateral sclerosis behavioral variant biomarker blood plasma blood serum brain cerebrospinal fluid cortical tissue frontotemporal dementia frontotemporal lobar degeneration Microrna primary progressive aphasia

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Microrna is a potential target for therapies to improve the physiological function of skeletal muscle after trauma

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Neural Regeneration Research 2022年第7期17卷 1617-1622页

作者： Xin-Yi Gu Bo Jin Zhi-Dan Qi Xiao-Feng Yin Department of Orthopedics and Traumatology Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) BeijingChina Department of Orthopedics The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu ProvinceChina

Micrornas can regulate the function of ion channels in many organs.Based on our previous study we propose that miR-142a-39,which is highly expressed in denervated skeletal muscle,might affect cell excitability through similar mechanisms.In this study,we overexpressed or knocked down miR-142a-3p in C2C12 cells using a lentivirus method.After 7 days of differentiation culture,whole-cell currents were recorded.The results showed that overexpression of miR-142a-3p reduced the cell membrane capacitance,increased potassium current density and decreased calcium current density.Knockdown of miR-142a-3p reduced sodium ion channel current density.The results showed that change in miR-142a-3p expression affected the ion channel currents in C2C12 cells,suggesting its possible roles in muscle cell electrophysiology.This study was approved by the Animal Ethics Committee of Peking University in July 2020(approval No.LA2017128).

关键词： C2C12 denervation ion channels Microrna miR-142a-3p muscle patch clamp potassium sodium whole-cell currents

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Microrna regulates the toxicological mechanism of four mycotoxins in vivo and in vitro

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Journal of Animal Science and Biotechnology 2022年第4期13卷 923-934页

作者： Jia Chen Shuhua Yang Peng Li Aibo Wu Eugenie Nepovimova Miao Long Wenda Wu Kamil Kuca College of Animal Science&Veterinary Medicine Shenyang Agricultural UniversityShenyang 110866China SIBS-UGENT-SJTU Joint Laboratory of Mycotoxin Research CAS Key Laboratory of NutritionMetabolism and Food SafetyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Department of Chemistry Faculty of ScienceUniversity of Hradec KraloveHradec Kralove 50003Czech Republic MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary MedicineNanjing Agricultural UniversityNanjing 210095China Biomedical Research Center University Hospital Hradec KraloveHradec Kralove 50003Czech Republic.

Mycotoxins can cause body poisoning and induce carcinogenesis,often with a high mortality rate.Therefore,it is of great significance to seek new targets that indicate mycotoxin activity and to diagnose and intervene in mycotoxin-induced diseases in their early stages.Micrornas(miRNAs)are physiological regulators whose dysregulation is closely related to the development of diseases.They are thus important markers for the occurrence and development of diseases.In this review,consideration is given to the toxicological mechanisms associated with four major mycotoxins(ochratoxin A,aflatoxin B1,deoxynivalenol,and zearalenone).The roles that miRNAs play in these mechanisms and the interactions between them and their target genes are explained,and summarize the important role of histone modifications in their toxicity.As a result,the ways that miRNAs are regulated in the pathogenicity signaling pathways are revealed which highlights the roles played by miRNAs in preventing and controlling the harmful effects of the mycotoxins.It is hoped that this review will provide a theoretical basis for the prevention and control of the damage caused by these mycotoxins.

关键词： Histone Methylation Microrna Mycotoxin

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Microrna expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches

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Neural Regeneration Research 2022年第4期17卷 728-740页

作者： Bridget Martinez Philip V.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

A review of recent animal models of amyotrophic lateral sclerosis showed a large number of mi RNAs had altered levels of expression in the brain and spinal cord,motor neurons of spinal cord and brainstem,and hypoglossal,facial,and red motor nuclei and were mostly upregulated.Among the mi RNAs found to be upregulated in two of the studies were mi R-21,mi R-155,mi R-125 b,mi R-146 a,mi R-124,mi R-9,and mi R-19 b,while those downregulated in two of the studies included mi R-146 a,mi R-29,mi R-9,and mi R-125 b.A change of direction in mi RNA expression occurred in some tissues when compared(e.g.,mi R-29 b-3 p in cerebellum and spinal cord of wobbler mice at 40 days),or at different disease stages(e.g.,mi R-200 a in spinal cord of SOD1(G93 A)mice at 95 days vs.108 and 112 days).In the animal models,suppression of mi R-129-5 p resulted in increased lifespan,improved muscle strength,reduced neuromuscular junction degeneration,and tended to improve motor neuron survival in the SOD1(G93 A)mouse model.Suppression of mi R-155 was also associated with increased lifespan,while lowering of mi R-29 a tended to improve lifespan in males and increase muscle strength in SOD1(G93 A)mice.Overexpression of members of mi R-17~92 cluster improved motor neuron survival in SOD1(G93 A)mice.Treatment with an artificial mi RNA designed to target h SOD1 increased lifespan and improved muscle strength in SOD1(G93 A)animals.Further studies with animal models of amyotrophic lateral sclerosis are warranted to validate these findings and identify specific mi RNAs whose suppression or directed against h SOD1 results in increased lifespan,improved muscle strength,reduced neuromuscular junction degeneration,and improved motor neuron survival in SOD1(G93 A)animals.

关键词： amyotrophic lateral sclerosis animal model brain brainstem Microrna motor neuron degeneration spinal cord therapeutic approaches

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卵泡液细胞外囊泡携带的Microrna对卵泡闭锁影响的研究进展

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生物工程学报 2022年第8期38卷 2767-2783页

作者：王莹王晓梅赵蕴琦吴盛辉张涌权富生西北农林科技大学动物医学院农业农村部动物生物技术重点实验室陕西杨凌712100

细胞外囊泡(extracellular vesicles,EVs)是细胞主动释放的膜结合颗粒。在原核生物和真核生物中,EVs被认为是细胞间进行信息交流的一种方式。EVs具有携带蛋白质、脂质和核酸等生物大分子的能力,可以影响亲本细胞和受体细胞的不同生理功... 详细信息

细胞外囊泡(extracellular vesicles,EVs)是细胞主动释放的膜结合颗粒。在原核生物和真核生物中,EVs被认为是细胞间进行信息交流的一种方式。EVs具有携带蛋白质、脂质和核酸等生物大分子的能力,可以影响亲本细胞和受体细胞的不同生理功能。其中,EVs携带的Microrna研究报道最多,在生物体生理功能方面发挥着重要作用。卵泡在发育过程中,只有少数卵泡可以充分发育、成熟、排卵,大多数卵泡在发育的不同阶段发生闭锁。在卵泡发育的整个过程中,每一阶段的变化以及卵泡闭锁调控机制还不完全清楚。本文在总结EVs类型、特性、分离方法及用途的基础上,从不同细胞因子、激素方面重点论述了卵泡液中EVs携带的Microrna是如何调控卵泡闭锁,同时对卵泡液EVs携带的Microrna在生殖调控和生殖疾病诊断方面的研究前景进行了展望,对于卵泡发育调控研究以及有效利用研究具有一定参考意义。

关键词：卵泡液细胞外囊泡 Microrna 卵泡闭锁

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新疆哈萨克族原发性高血压患者外周血淋巴细胞微小RNA表达谱的生物信息学分析

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生理学报 2022年第5期74卷 751-762页

作者：王彦张亮杨瑞单莉娅王璐张莹莹李新芝马克涛石河子大学医学院新疆地方与民族高发病教育部重点实验室石河子832000 石河子大学医学院国家卫健委中亚高发病防治重点实验室石河子832000 石河子大学医学院生理学教研室石河子832000 石河子大学医学院病理生理学教研室石河子832000

本研究旨在探讨新疆哈萨克族原发性高血压患者和健康者外周血淋巴细胞中微小RNA(Microrna,miRNA)差异表达谱,为高血压的发生机制研究提供理论基础。将2016年4月至2019年5月新疆石河子大学医学院第一附属医院心内科住院部及门诊就诊的30... 详细信息

本研究旨在探讨新疆哈萨克族原发性高血压患者和健康者外周血淋巴细胞中微小RNA(Microrna,miRNA)差异表达谱,为高血压的发生机制研究提供理论基础。将2016年4月至2019年5月新疆石河子大学医学院第一附属医院心内科住院部及门诊就诊的30例哈萨克族原发性高血压患者作为高血压组,将30例哈萨克族健康者作为对照组。比较6个哈萨克族高血压患者与6个配对的正常血压者外周血淋巴细胞中miRNA表达谱,对差异表达的miRNA进行聚类、GSEA富集、靶基因预测和靶基因注释等生物信息学分析,并进行qRT-PCR验证。结果显示,与对照组相比,高血压组筛选出73个差异表达miRNA,其中39个miRNA表达上调,34个miRNA表达下调;通过GSEA富集分析共筛选出11个与高血压相关的miRNA,分别是hsamiR-100-5p、hsa-miR-150-5p、hsa-miR-299-5p、hsa-miR-299-3p、hsa-miR-296-5p、hsa-miR-196b-5p、hsa-miR-503-5p、hsamiR-628-5p、hsa-miR-874-3p、hsa-miR-543、hsa-miR-940。通过qRT-PCR检验发现,与对照组相比,高血压组hsa-miR-100-5p、hsa-miR-299-5p、hsa-miR-299-3p、hsa-miR-196b-5p、hsa-miR-503-5p、hsa-miR-628-5p、hsa-miR-543表达上调,hsamiR-150-5p、hsa-miR-296-5p、hsa-miR-874-3p、hsa-miR-940表达下调。基因芯片中的表达趋势和qRT-PCR验证结果一致。利用在线数据库对11个与高血压相关的miRNA进行预测,共预测出1647个靶基因;GO功能富集分析显示,在生物过程方面,高血压相关靶基因主要与神经系统发育、细胞定位、细胞代谢过程的调节、神经元的产生以及生物过程的正调控等方面相关;在细胞组成方面,主要与膜界细胞器、细胞质、细胞内膜结合的细胞器、突触部分、神经元部分、核质等相关;在分子功能方面,主要与蛋白质结合、转录调控区DNA结合、RNA聚合酶II调节区DNA结合、转录调节活性、离子结合等方面相关;KEGG富集分析显示p53信号通路、心肌细胞中的肾上腺素能信号、cAMP信号通路、内分泌和其他因子调节的钙重吸收、mTOR信号通路、醛固酮调节的钠重吸收、TGF-β信号通路可能与高血压的发生和发展相关。以上结果提示,哈萨克族原发性高血压患者与健康者外周血淋巴细胞中miRNA表达存在差异,筛选出的miRNA可能与哈萨克族原发性高血压的发生和发展相关,其在高血压中的作用机制有待进一步探索验证。

关键词：高血压哈萨克族淋巴细胞 Microrna 表达谱生物信息学分析

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Microrna-149 Regulates Proliferation,Migration,and Invasion of Pituitary Adenoma Cells by Targeting ADAM12 and MMP14

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Current Medical Science 2022年第6期42卷 1131-1139页

作者： Zhuo ZHANG Agnes Schäfer Benjamin Voellger Jun-wen WANG Ting LEI Christopher Nimsky Jörg W.Bartsch Department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Neurosurgery Philipps University MarburgBaldingerstrasseMarburg35033Germany Sino-German Neuro-Oncology Molecular Laboratory Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Center for Mind Brainand BehaviorHans-Meerwein-Strasse 6Marburg35032Germany

Objective Pituitary adenomas(PAs)can adapt an aggressive phenotype by invading adjacent brain structures with rapid cellular proliferation.Previous studies demonstrated that excessive expression of metalloproteases ADAM12 and MMP-14 is instrumental for the active proliferation and invasiveness of PA cells in vitro and of tumors in vivo.However,the mechanisms regulating ADAM12 and MMP-14 expression in PAs remain unclear.Methods Target gene prediction and transcriptomic profiling of invasive vs.noninvasive human PA samples were performed to identify miRNA species potentially involved in the regulation of ADAM12 and MMP14.For cellular analyses of miRNA functions,two mouse PA cell lines(AtT20 and TtT/GF)were transfected with miR-149-3p and miR-149-5p,respectively.The effects of miR-149(3p and 5p)on expression levels of ADAM12 and MMP14 were determined by Western blotting followed by an analysis of proliferation and colony formation assays,scratch migration assays,and invasion assays.Results A significant downregulation of miRNA-149 was observed in invasive vs.noninvasive PA(0.32 vs.0.09,P<0.0001).In AtT-20 and TtT/GF mouse PAs cells,transfection of mimic miRNA-149(3p and 5p)caused a significantly reduced cell proliferation and matrigel invasion,whilst the effect on cell migration was less pronounced.Both strands of miRNA-149(3p and 5p)markedly reduced protein levels of ADAM12 and MMP-14 by at least 40%in both cell lines.Conclusion This study proved that the invasiveness of PA cells is,at least partly,regulated by miRNA-149-dependent expression of ADAM12 and MMP-14.

关键词： pituitary adenoma Microrna miRNA-149 ADAM12 MMP-14 invasion

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