Objective: To investigate the differential expression of miRNA and related biological functions and signaling pathways after the intervention of the THP-1-derived foam cell model with the drug-containing serum of Yima...Objective: To investigate the differential expression of miRNA and related biological functions and signaling pathways after the intervention of the THP-1-derived foam cell model with the drug-containing serum of Yimaijiangzhi Decoction. Methods: The experiment was divided into macrophage group, foam cell model group and Yimaijiangzhi drug-containing serum group. THP-1 cells were induced into macrophages by Fopol ester, and induced differentiated macrophages were given ox-LDL to establish foam cell model, and Yimaijiangzhi decoction rat serum was used to intervene the foam cells. Total RNA was extracted from cells in each group for miRNA sequencing, differential expression of miRNA was screened, and relevant target genes were predicted for GO analysis and KEGG analysis, protein interaction network and miRNA-target gene interaction network were established, and RT-qPCR was used to verify the possible signaling pathways for improving atherosclerosis. Result: The difference miRNA between blank group and model group was hsa-miR-302c-3p, hsa-miR-302d-3p, hsa- mir-30d-3p, hsa-mir-3189-3p, hsa-mir-374b-5p, hsa-mir-423-5p, hsa-mir-423-5p, and hsa- mir-4781-3p, hsa-mir-663a;The miRNAs of model group and Yimaijiangzhi drug-containing serum group were hsa-mir-3150a-3p, hsa-mir-7704, hsa-mir-887-3p, hsa-mir-150-5p, hsa- mir-423-5p, hsa-mir-374c-3p, hsa-mir-374c-3p, hsa-mir-374b-5p;The difference of miRNAs prediction target genes between model group and Yimaijiangzhi drug-containing serum group showed that the miRNA prediction target genes were mainly enriched in MAPK signaling pathway, ErbB signaling pathway, Hippo signaling pathway, Wnt signaling pathway and other signaling pathways. SCN1A, PRKACA, MECP2, EIF4E, SRSF1, MBNL1, PRKCA, PPARGC1A may be the potential key targets for the effect of the drug-containing serum of Yimaijiangzhi Decoction on THP-1-derived foam cells. Conclusion: hsa-mir-374c-3p, hsa- mir-423-5p, and hsa-mir-374b-5p are important miRNAs that the drug-containing serum of Yimaijiangzhi Decoction acts on foam cells. The significantly differentially expressed mirnas and significantly enriched related signaling pathways may provide new ideas for the diagnosis and treatment of atherosclerosis.展开更多
MicroRNAs（miRNAs）are small noncoding RNAs of 19-24 nt and play important roles in post-transcriptional regulation of gene expression（Baek et al.,2008;Zhou et al.,2011）and various biological processes including gro...MicroRNAs（miRNAs）are small noncoding RNAs of 19-24 nt and play important roles in post-transcriptional regulation of gene expression（Baek et al.,2008;Zhou et al.,2011）and various biological processes including growth,展开更多
A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan,but the underlying mechanisms for these observations are largely unknown.Particularly,it is not known whether a longterm vege...A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan,but the underlying mechanisms for these observations are largely unknown.Particularly,it is not known whether a longterm vegetarian dietary pattern may affect the circulating miRNA expression in such a way as to modulate the healthspan.The Adventist Health Study-2(AHS-2)cohort includes a large number of older adults who primarily follow vegetarian dietary patterns and reside in Loma Linda,California,one of five“Blue Zones”in the world in which a higher proportion of the population enjoys a longer than average lifespan.We performedmiRNA-seq in 96 subjects selected from the AHS-2 cohort with different dietary patterns.We identified several differentially expressed miRNAs between vegetarians and non-vegetarians,which are involved in immune response and cytokine signaling,cell growth and proliferation as well as age-related diseases such as cardiovascular diseases and neurodegenerative diseases.Overall,our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs,which may be related in a beneficial manner to the healthspan.Further investigation is needed to validate these miRNAs as potential biomarkers for diet-modulated longevity in humans.展开更多
MicroRNAs(miRNAs) are small non-coding RNAs that regulate a variety of biological processes. miRNA expression often exhibits spatial and temporal specificity. However, genome-wide miRNA expression patterns in differen...MicroRNAs(miRNAs) are small non-coding RNAs that regulate a variety of biological processes. miRNA expression often exhibits spatial and temporal specificity. However, genome-wide miRNA expression patterns in different organs during development of Arabidopsis thaliana have not yet been systemically investigated. In this study, we sequenced small RNA libraries generated from 27 different organ/tissue types, which cover the entire life cycle of Arabidopsis. Analysis of the sequencing data revealed that most miRNAs are ubiquitously expressed, whereas a small set of miRNAs display highly specific expression patterns. In addition, different miRNA members within the same family have distinct spatial and temporal expression patterns. Moreover, we found that some miRNAs are produced from different arms of their hairpin precursors at different developmental stages. This work provides new insights into the regulation of miRNA biogenesis and a rich resource for future investigation of miRNA functions in Arabidopsis.展开更多
Doxorubicin(DOx)is the most effective chemotherapeutic for breast cancer,but it is usually associated with severe cardiotoxicity.Further investigation to alleviate its side effects is essential.The present study inves...Doxorubicin(DOx)is the most effective chemotherapeutic for breast cancer,but it is usually associated with severe cardiotoxicity.Further investigation to alleviate its side effects is essential.The present study investigated the mechanism of the cross-organ communication between tumors and the heart and potential intervention targets.Morphological bubble-like protrusions were observed in both adult murine ventricular cardiomyocytes(AMvCs)and human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)cocultured with breast cancer cells(BCCs),along with elevated expression of pyroptosis-related proteins.Exosomes(EXOs)from DOX-treated BCCs aggravated DOX-induced cardiotoxicity(DOXIC)in an orthotopic mouse model of breast cancer.Blocking miRNAs by knocking down Rab27a or inhibiting the release of EXOs in cancer tissue by Dicer enzyme knockout attenuated this additional injury effect.Exosomal miRNA sequencing revealed that miR-216a-5p is especially upregulated in EXOs from DOX-induced BCCs.Mechanistically,miR-216a-5p was upregulated by enhanced transcription mediated by DOXinduced AMP-dependent transcription factor 3(ATF3)and packaged into EXOs by splicing factor 3b subunit 4(SF3B4)in BCCs.Itchy E3 ubiquitin-protein ligase(ITCH)was identified as a novel downstream target mRNA of miR-216a-5p.ITCH negatively mediated thioredoxin-interacting protein(TXNIP)ubiquitination to activate the NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)inflammasome pathway,ultimately leading to cardiomyocyte pyroptosis.Our findings revealed novel cross-organ pathogenic communication between breast cancer and the heart through the exosomal miR-216a-5p-mediated ITCH/TXNIP/NLRP3 pathway,which drives cardiomyocyte pyroptosis.These findings suggest that targeting myocardial miR-216a-5p or blocking harmful EXOs from breast cancer is a potential therapeutic strategy for alleviating DOXIC.展开更多
基金Guangxi Natural Science Foundation(No.2020GXNSFAA297158)The Fifth Batch of National Clinical Excellent Talent Training Projects[Guozhong Pharmaceutical Education(2022)No.1]+1 种基金Guangxi Youth Qihuang Scholar Training Program[Guizhong Medical Science and Education Development(2022)No.13]Guangxi Graduate Education Innovation Program Project(No.YCSW2022340)。
文摘Objective: To investigate the differential expression of miRNA and related biological functions and signaling pathways after the intervention of the THP-1-derived foam cell model with the drug-containing serum of Yimaijiangzhi Decoction. Methods: The experiment was divided into macrophage group, foam cell model group and Yimaijiangzhi drug-containing serum group. THP-1 cells were induced into macrophages by Fopol ester, and induced differentiated macrophages were given ox-LDL to establish foam cell model, and Yimaijiangzhi decoction rat serum was used to intervene the foam cells. Total RNA was extracted from cells in each group for miRNA sequencing, differential expression of miRNA was screened, and relevant target genes were predicted for GO analysis and KEGG analysis, protein interaction network and miRNA-target gene interaction network were established, and RT-qPCR was used to verify the possible signaling pathways for improving atherosclerosis. Result: The difference miRNA between blank group and model group was hsa-miR-302c-3p, hsa-miR-302d-3p, hsa- mir-30d-3p, hsa-mir-3189-3p, hsa-mir-374b-5p, hsa-mir-423-5p, hsa-mir-423-5p, and hsa- mir-4781-3p, hsa-mir-663a;The miRNAs of model group and Yimaijiangzhi drug-containing serum group were hsa-mir-3150a-3p, hsa-mir-7704, hsa-mir-887-3p, hsa-mir-150-5p, hsa- mir-423-5p, hsa-mir-374c-3p, hsa-mir-374c-3p, hsa-mir-374b-5p;The difference of miRNAs prediction target genes between model group and Yimaijiangzhi drug-containing serum group showed that the miRNA prediction target genes were mainly enriched in MAPK signaling pathway, ErbB signaling pathway, Hippo signaling pathway, Wnt signaling pathway and other signaling pathways. SCN1A, PRKACA, MECP2, EIF4E, SRSF1, MBNL1, PRKCA, PPARGC1A may be the potential key targets for the effect of the drug-containing serum of Yimaijiangzhi Decoction on THP-1-derived foam cells. Conclusion: hsa-mir-374c-3p, hsa- mir-423-5p, and hsa-mir-374b-5p are important miRNAs that the drug-containing serum of Yimaijiangzhi Decoction acts on foam cells. The significantly differentially expressed mirnas and significantly enriched related signaling pathways may provide new ideas for the diagnosis and treatment of atherosclerosis.
基金partly supported by the National Natural Science Foundation of China(Nos.61572363,91530321 and 61602347)the Natural Science Foundation of Shanghai(No.17ZR1445600)City University of Hong Kong(No.7004707)
文摘MicroRNAs（miRNAs）are small noncoding RNAs of 19-24 nt and play important roles in post-transcriptional regulation of gene expression（Baek et al.,2008;Zhou et al.,2011）and various biological processes including growth,
基金The genomic work carried out at the Loma Linda University Center for Genomics were funded in part by the National Institutes of Health(NIH)(Grant No.S10OD019960)(CW)This project is partially supported by the American Heart Association(AHA)(Grant No.18IPA34170301)(CW)+1 种基金and also partially supported by NIH(Grants No.HL115195-06(HQ)/subcontract(GSU)#SP00013920-02(CW),and HL137962(HQ)/subcontract(GSU)#SP00013696-01(CW))Subject recruitment and blood collection were partially funded by the LLU Grants for Research and School Partnerships(GRASP)2140309(NG&GL).
文摘A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan,but the underlying mechanisms for these observations are largely unknown.Particularly,it is not known whether a longterm vegetarian dietary pattern may affect the circulating miRNA expression in such a way as to modulate the healthspan.The Adventist Health Study-2(AHS-2)cohort includes a large number of older adults who primarily follow vegetarian dietary patterns and reside in Loma Linda,California,one of five“Blue Zones”in the world in which a higher proportion of the population enjoys a longer than average lifespan.We performedmiRNA-seq in 96 subjects selected from the AHS-2 cohort with different dietary patterns.We identified several differentially expressed miRNAs between vegetarians and non-vegetarians,which are involved in immune response and cytokine signaling,cell growth and proliferation as well as age-related diseases such as cardiovascular diseases and neurodegenerative diseases.Overall,our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs,which may be related in a beneficial manner to the healthspan.Further investigation is needed to validate these miRNAs as potential biomarkers for diet-modulated longevity in humans.
基金supported by grants fromNational Key Research and Development Program of China (2016YFA0500800)National Natural Science Foundation of China (31421001, 31225015) to Yijun Qi
文摘MicroRNAs(miRNAs) are small non-coding RNAs that regulate a variety of biological processes. miRNA expression often exhibits spatial and temporal specificity. However, genome-wide miRNA expression patterns in different organs during development of Arabidopsis thaliana have not yet been systemically investigated. In this study, we sequenced small RNA libraries generated from 27 different organ/tissue types, which cover the entire life cycle of Arabidopsis. Analysis of the sequencing data revealed that most miRNAs are ubiquitously expressed, whereas a small set of miRNAs display highly specific expression patterns. In addition, different miRNA members within the same family have distinct spatial and temporal expression patterns. Moreover, we found that some miRNAs are produced from different arms of their hairpin precursors at different developmental stages. This work provides new insights into the regulation of miRNA biogenesis and a rich resource for future investigation of miRNA functions in Arabidopsis.
基金supported by the National Key Research and Development Plan(2022YFA1104500,2022YFC3602400,2022YFA1104704)the National Nature Science Foundation of China(82470366,82270380,82470379)+2 种基金Beijing Natural Science Foundation(7232159)Beijing Nova Program(Z211100002121048)the Joint Fundof Beijing Natural Science Foundation(L241026).
文摘Doxorubicin(DOx)is the most effective chemotherapeutic for breast cancer,but it is usually associated with severe cardiotoxicity.Further investigation to alleviate its side effects is essential.The present study investigated the mechanism of the cross-organ communication between tumors and the heart and potential intervention targets.Morphological bubble-like protrusions were observed in both adult murine ventricular cardiomyocytes(AMvCs)and human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)cocultured with breast cancer cells(BCCs),along with elevated expression of pyroptosis-related proteins.Exosomes(EXOs)from DOX-treated BCCs aggravated DOX-induced cardiotoxicity(DOXIC)in an orthotopic mouse model of breast cancer.Blocking miRNAs by knocking down Rab27a or inhibiting the release of EXOs in cancer tissue by Dicer enzyme knockout attenuated this additional injury effect.Exosomal miRNA sequencing revealed that miR-216a-5p is especially upregulated in EXOs from DOX-induced BCCs.Mechanistically,miR-216a-5p was upregulated by enhanced transcription mediated by DOXinduced AMP-dependent transcription factor 3(ATF3)and packaged into EXOs by splicing factor 3b subunit 4(SF3B4)in BCCs.Itchy E3 ubiquitin-protein ligase(ITCH)was identified as a novel downstream target mRNA of miR-216a-5p.ITCH negatively mediated thioredoxin-interacting protein(TXNIP)ubiquitination to activate the NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)inflammasome pathway,ultimately leading to cardiomyocyte pyroptosis.Our findings revealed novel cross-organ pathogenic communication between breast cancer and the heart through the exosomal miR-216a-5p-mediated ITCH/TXNIP/NLRP3 pathway,which drives cardiomyocyte pyroptosis.These findings suggest that targeting myocardial miR-216a-5p or blocking harmful EXOs from breast cancer is a potential therapeutic strategy for alleviating DOXIC.
