Pub Date : 2022-04-22DOI: 10.2174/2211536611666220422123437
P. Postnikov, Y. Efimova, I. Pronina
BACKGROUND The analysis of individual microRNAs (miRNAs) as a diagnostic and prognostic tool for the effective treatment of various diseases has aroused particular interest in the scientific community. The determination of circulating miRNAs makes it possible to assess biological changes associated with nutritional processes, the intake of dietary supplements and drugs, etc. The profile of circulating miRNAs reflects the individual adaptation of the organism to the effect of specific environmental conditions. OBJECTIVE to systematize the data and show the importance of circulating miRNAs as new potential biomarkers of the organism's response to the intake of various dietary supplements, drugs, and consider the possibility of their use in doping control. METHOD a systematic analysis of scientific publications (ncbi.nlm.nih.gov) on the miRNA expression profile in response to the intake of dietary supplements and drugs most often used by athletes, and supposed their role as potential markers in modern doping control was carried out. RESULTS the profile of circulating miRNAs is highly dependent on the intake of a particular drug, and, therefore, may be used as a marker of the effects of biologically active supplements and drugs including the substances from the Prohibited List of the World Anti-Doping Agency (WADA). CONCLUSION monitoring of circulating miRNAs can serve as a high-precision marker for detecting doping abuse in elite sports. However, it is necessary to conduct additional studies on the effect of complex drugs on the profile of circulating miRNAs and individual circulating miRNAs on a particular biological process.
{"title":"Circulating MicroRNAs as a New Class of Biomarkers of Physiological Reactions of the Organism to the Intake of Dietary Supplements and Drugs.","authors":"P. Postnikov, Y. Efimova, I. Pronina","doi":"10.2174/2211536611666220422123437","DOIUrl":"https://doi.org/10.2174/2211536611666220422123437","url":null,"abstract":"BACKGROUND\u0000The analysis of individual microRNAs (miRNAs) as a diagnostic and prognostic tool for the effective treatment of various diseases has aroused particular interest in the scientific community. The determination of circulating miRNAs makes it possible to assess biological changes associated with nutritional processes, the intake of dietary supplements and drugs, etc. The profile of circulating miRNAs reflects the individual adaptation of the organism to the effect of specific environmental conditions.\u0000\u0000\u0000OBJECTIVE\u0000to systematize the data and show the importance of circulating miRNAs as new potential biomarkers of the organism's response to the intake of various dietary supplements, drugs, and consider the possibility of their use in doping control.\u0000\u0000\u0000METHOD\u0000a systematic analysis of scientific publications (ncbi.nlm.nih.gov) on the miRNA expression profile in response to the intake of dietary supplements and drugs most often used by athletes, and supposed their role as potential markers in modern doping control was carried out.\u0000\u0000\u0000RESULTS\u0000the profile of circulating miRNAs is highly dependent on the intake of a particular drug, and, therefore, may be used as a marker of the effects of biologically active supplements and drugs including the substances from the Prohibited List of the World Anti-Doping Agency (WADA).\u0000\u0000\u0000CONCLUSION\u0000monitoring of circulating miRNAs can serve as a high-precision marker for detecting doping abuse in elite sports. However, it is necessary to conduct additional studies on the effect of complex drugs on the profile of circulating miRNAs and individual circulating miRNAs on a particular biological process.","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48594451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-13DOI: 10.2174/2211536611666220413100636
Ravi Bhushan, A. Rani, D. Gupta, Akhtar Ali, P. Dubey
BACKGROUND Small non-coding micro RNAs (miRNAs) are indicated in various metabolic processes and play a critical role in disease pathology, including gestational diabetes mellitus (GDM). OBJECTIVE The purpose of this study was to examine the altered expression of miRNAs and their target genes in placental tissue (PL), cord blood (CB), and maternal blood (MB) of matched non-glucose tolerant (NGT) and GDM mother. METHODS In a case-control study, micro-RNA was quantified from forty-five serum (MB n = 15, CB n = 15, and PL n = 15) and matched placental tissue using stem-loop RT-qPCR followed by target prediction, network construction and functional and pathways enrichment analysis. Further, target genes were verified in-vitro through transfection and RT-qPCR. RESULTS Five miRNAs, namely hsa-let 7a-5P, hsa-miR7-5P, hsa-miR9-5P, hsa-miR18a-5P, and hsa-miR23a-3P were significantly over-expressed (p < 0.05) in all three samples namely PL, CB, and MB of GDM patients. However, the sample-wise comparison reveals higher expression of miRNA 7 in MB while lowest in CB than control. Furthermore, a comparison of fold change expression of target genes discloses a lower expression of IRS1, IRS2, and RAF1 in MB while comparatively higher expression of NRAS in MB and CB. In-vitro validation reveals lower expression of IRS1/2 and RAF1 in response to overexpression of miR-7 and vice-versa. Thus it is evident that increased miRNA7 expression causes down-regulation of its target genes IRS1, IRS2, and RAF1 in GDM mother compared to control. Further, target prediction, pathway enrichment, and hormone analysis (significantly higher FSH & LH in MB of GDM compared to NGT) revealed the insulin signaling, inflammatory and GnRH signaling as major pathways regulated by miRNA7. CONCLUSIONS Thus, an elevated level of miRNA7 may be associated with the progression of GDM by altering the multiple pathways like insulin, GnRH, and inflammatory signaling pathways via targeting IRS1, IRS2, and RAF1, implicating a new therapeutic target for GDM.
小的非编码微rna (miRNAs)参与多种代谢过程,并在包括妊娠糖尿病(GDM)在内的疾病病理中发挥关键作用。目的研究非糖耐量(NGT)和GDM配对的母亲胎盘组织(PL)、脐带血(CB)和母体血(MB)中miRNAs及其靶基因的表达变化。方法采用茎环RT-qPCR方法,对45例血清(MB n = 15, CB n = 15, PL n = 15)和匹配胎盘组织的微rna进行定量分析,并进行靶标预测、网络构建、功能和途径富集分析。进一步,通过转染和RT-qPCR对靶基因进行体外验证。结果hsa-let 7a-5P、hsa-miR7-5P、hsa-miR9-5P、hsa-miR18a-5P、hsa-miR23a-3P 5种mirna在GDM患者PL、CB和MB中均显著过表达(p < 0.05)。然而,样本比较显示,miRNA - 7在MB中的表达高于对照组,而在CB中的表达低于对照组。此外,通过比较靶基因的折叠变化表达,发现MB中IRS1、IRS2和RAF1的表达较低,而MB和CB中NRAS的表达相对较高。体外验证显示,miR-7过表达会导致IRS1/2和RAF1的低表达,反之亦然。由此可见,在GDM母鼠中,miRNA7表达增加导致其靶基因IRS1、IRS2和RAF1较对照下调。此外,靶标预测、途径富集和激素分析(GDM的MB中FSH和LH明显高于NGT)显示,胰岛素信号、炎症和GnRH信号是miRNA7调节的主要信号通路。因此,miRNA7水平升高可能通过靶向IRS1、IRS2和RAF1改变胰岛素、GnRH和炎症信号通路等多种途径与GDM的进展相关,提示GDM的新治疗靶点。
{"title":"MicroRNA-7 regulates insulin signaling pathway by targeting IRS1, IRS2, and RAF1 genes in gestational diabetes mellitus.","authors":"Ravi Bhushan, A. Rani, D. Gupta, Akhtar Ali, P. Dubey","doi":"10.2174/2211536611666220413100636","DOIUrl":"https://doi.org/10.2174/2211536611666220413100636","url":null,"abstract":"BACKGROUND\u0000Small non-coding micro RNAs (miRNAs) are indicated in various metabolic processes and play a critical role in disease pathology, including gestational diabetes mellitus (GDM).\u0000\u0000\u0000OBJECTIVE\u0000The purpose of this study was to examine the altered expression of miRNAs and their target genes in placental tissue (PL), cord blood (CB), and maternal blood (MB) of matched non-glucose tolerant (NGT) and GDM mother.\u0000\u0000\u0000METHODS\u0000In a case-control study, micro-RNA was quantified from forty-five serum (MB n = 15, CB n = 15, and PL n = 15) and matched placental tissue using stem-loop RT-qPCR followed by target prediction, network construction and functional and pathways enrichment analysis. Further, target genes were verified in-vitro through transfection and RT-qPCR.\u0000\u0000\u0000RESULTS\u0000Five miRNAs, namely hsa-let 7a-5P, hsa-miR7-5P, hsa-miR9-5P, hsa-miR18a-5P, and hsa-miR23a-3P were significantly over-expressed (p < 0.05) in all three samples namely PL, CB, and MB of GDM patients. However, the sample-wise comparison reveals higher expression of miRNA 7 in MB while lowest in CB than control. Furthermore, a comparison of fold change expression of target genes discloses a lower expression of IRS1, IRS2, and RAF1 in MB while comparatively higher expression of NRAS in MB and CB. In-vitro validation reveals lower expression of IRS1/2 and RAF1 in response to overexpression of miR-7 and vice-versa. Thus it is evident that increased miRNA7 expression causes down-regulation of its target genes IRS1, IRS2, and RAF1 in GDM mother compared to control. Further, target prediction, pathway enrichment, and hormone analysis (significantly higher FSH & LH in MB of GDM compared to NGT) revealed the insulin signaling, inflammatory and GnRH signaling as major pathways regulated by miRNA7.\u0000\u0000\u0000CONCLUSIONS\u0000Thus, an elevated level of miRNA7 may be associated with the progression of GDM by altering the multiple pathways like insulin, GnRH, and inflammatory signaling pathways via targeting IRS1, IRS2, and RAF1, implicating a new therapeutic target for GDM.","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42706551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-18DOI: 10.2174/2211536611666220318142031
Toral Manvar, Naman Mangukia, Saumya K. Patel, Rakesh M. Rawal
BACKGROUND Since ancient times, "betel leaf" (Piper betle) has been revered for its religious, cultural, and medicinal properties. Phytochemicals from the Piper betle are effective in a variety of conditions, including cancer. To date, however, no genomic study or evidence has been found to elucidate the regulatory mechanism that underpins its therapeutic properties. This is the first study of its kind to predict Piper betle miRNAs and also the first genomics source representation of Piper betle. According to previous research, miRNAs from the plants we eat can regulate gene expression. In line with this, our in-silico study revealed that Piper betle and human cross-kingdom control occurs. METHOD This study demonstrates the prediction and in-silico validation of Piper betle miRNAs from NGS-derived transcript sequences. The cross-kingdom regulation which can also be understood as inter-species RNA regulation was studied to identify human mRNA targets being controlled by Piper betle miRNAs. Functional annotation and gene-disease association of human targets were performed to understand the role of Piper betle miRNAs in human health and disease. The protein-protein interaction and expression study of targets was further carried out to decipher their role in cancer development. RESULTS Identified six Piper betle miRNAs belonging to miR156, miR164, miR172, and miR535 families were discovered to target 198 human mRNAs involved in various metabolic and disease processes. Angiogenesis and the cell surface signaling pathway were the most enriched gene ontology correlated with targets, both of which play a critical role in disease mechanisms, especially in the case of carcinoma. In an analysis of gene-disease interactions, 40 genes were found to be related to cancer. According to a protein-protein interaction, the CDK6 gene, which is thought to be a central regulator of cell cycle progression, was found as a hub protein, affecting the roles of CBFB, SAMD9, MDM4, AXIN2, and NOTCH2 onco genes. Further investigation revealed that pbe-miRNA164a can be used as a regulator to minimise disease severity in Acute Myeloid Leukemia, where CDK6 expression is highest compared to normal cells. CONCLUSION The predicted pbe-miRNA164a in this study can be a promising suppressor of CDK6 gene involved in tumour angiogenesis. In vivo validation of the pbe-miRNA164a mimic could pave the way for new opportunities to fight cancer and leverage the potential of Piper betle in the healthcare sector.
{"title":"Understanding the Molecular Mechanisms of Betel miRNAs on Human Health.","authors":"Toral Manvar, Naman Mangukia, Saumya K. Patel, Rakesh M. Rawal","doi":"10.2174/2211536611666220318142031","DOIUrl":"https://doi.org/10.2174/2211536611666220318142031","url":null,"abstract":"BACKGROUND\u0000Since ancient times, \"betel leaf\" (Piper betle) has been revered for its religious, cultural, and medicinal properties. Phytochemicals from the Piper betle are effective in a variety of conditions, including cancer. To date, however, no genomic study or evidence has been found to elucidate the regulatory mechanism that underpins its therapeutic properties. This is the first study of its kind to predict Piper betle miRNAs and also the first genomics source representation of Piper betle. According to previous research, miRNAs from the plants we eat can regulate gene expression. In line with this, our in-silico study revealed that Piper betle and human cross-kingdom control occurs.\u0000\u0000\u0000METHOD\u0000This study demonstrates the prediction and in-silico validation of Piper betle miRNAs from NGS-derived transcript sequences. The cross-kingdom regulation which can also be understood as inter-species RNA regulation was studied to identify human mRNA targets being controlled by Piper betle miRNAs. Functional annotation and gene-disease association of human targets were performed to understand the role of Piper betle miRNAs in human health and disease. The protein-protein interaction and expression study of targets was further carried out to decipher their role in cancer development.\u0000\u0000\u0000RESULTS\u0000Identified six Piper betle miRNAs belonging to miR156, miR164, miR172, and miR535 families were discovered to target 198 human mRNAs involved in various metabolic and disease processes. Angiogenesis and the cell surface signaling pathway were the most enriched gene ontology correlated with targets, both of which play a critical role in disease mechanisms, especially in the case of carcinoma. In an analysis of gene-disease interactions, 40 genes were found to be related to cancer. According to a protein-protein interaction, the CDK6 gene, which is thought to be a central regulator of cell cycle progression, was found as a hub protein, affecting the roles of CBFB, SAMD9, MDM4, AXIN2, and NOTCH2 onco genes. Further investigation revealed that pbe-miRNA164a can be used as a regulator to minimise disease severity in Acute Myeloid Leukemia, where CDK6 expression is highest compared to normal cells.\u0000\u0000\u0000CONCLUSION\u0000The predicted pbe-miRNA164a in this study can be a promising suppressor of CDK6 gene involved in tumour angiogenesis. In vivo validation of the pbe-miRNA164a mimic could pave the way for new opportunities to fight cancer and leverage the potential of Piper betle in the healthcare sector.","PeriodicalId":38067,"journal":{"name":"MicroRNA (Shariqah, United Arab Emirates)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43561084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}