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Microrna-670 aggravates cerebral ischemia/reperfusion injury via the Yap pathway

Neural Regeneration Research 2021年第6期16卷 1024-1030页

作者： Shi-Jia Yu Ming-Jun Yu Zhong-Qi Bu Ping-Ping He Juan Feng Department of Neurology Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of Neurosurgery Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Apoptosis is an important programmed cell death process involved in ischemia/reperfusion *** are considered to play an important role in the molecular mechanism underlying the regulation of cerebral ischemia and reperfusion ***,whether miR-670 can regulate cell growth and death in cerebral ischemia/reperfusion and the underlying mechanism are poorly *** this study,we established mouse models of transient middle artery occlusion and Neuro 2a cell models of oxygen-glucose deprivation and reoxygenation to investigate the potential molecular mechanism by which miR-670 exhibits its effects during cerebral ischemia/reperfusion injury both in vitro and in *** results showed that after ischemia/reperfusion injury,miR-670 expression was obviously *** miR-670 expression was inhibited with an miR-670 antagomir,cerebral ischemia/reperfusion injury-induced neuronal death was obviously *** miR-670 overexpression was induced by an miR-670 agomir,neuronal apoptosis was *** addition,we also found that miR-670 could promote Yap degradation via phosphorylation and worsen neuronal apoptosis and neurological *** of miR-670 reduced neurological impairments after cerebral ischemia/reperfusion *** results suggest that microrna-670 aggravates cerebral ischemia/reperfusion injury through the Yap pathway,which may be a potential target for treatment of cerebral ischemia/reperfusion *** present study was approved by the Institutional Animal Care and Use Committee of China Medical University on February 27,2017(IRB No.2017PS035K).

关键词： apoptosis cerebral ischemia and reperfusion injury microrna miR-670 neurological function neuron non-coding rna pathway

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Pharmacoepigenetics in type 2 diabetes: is it clinically relevant?

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DIABETOLOGIA 2022年第11期65卷 1849-1853页

作者： Ling, Charlotte Lund Univ Scania Univ Hosp Lund Univ Diabet Ctr Dept Clin SciEpigenet & Diabet Unit Malmo Sweden

Data generated over nearly two decades clearly demonstrate the importance of epigenetic modifications and mechanisms in the pathogenesis of type 2 diabetes. However, the role of pharmacoepigenetics in type 2 diabetes is less well established. The field of pharmacoepigenetics covers epigenetic biomarkers that predict response to therapy, therapy-induced epigenetic alterations as well as epigenetic therapies including inhibitors of epigenetic enzymes. Not all individuals with type 2 diabetes respond to glucose-lowering therapies in the same way, and there is therefore a need for clinically useful biomarkers that discriminate responders from non-responders. Blood-based epigenetic biomarkers may be useful for this purpose. There is also a need for a better understanding of whether existing glucose-lowering therapies exert their function partly through therapy-induced epigenetic alterations. Finally, epigenetic enzymes may be drug targets for type 2 diabetes. Here, I discuss whether pharmacoepigenetics is clinically relevant for type 2 diabetes based on studies addressing this topic.

关键词： Adipose tissue Beta cells Blood Blood-based epigenetic biomarkers DNA methylation Drug targets Epigenetic enzymes Epigenetics Histone modification Inhibitors Liver non-coding rna Pancreatic islets Pharmacogenetics Precision medicine Skeletal muscle

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Nanopore long-read rnaseq reveals regulatory mechanisms of thermally variable reef environments promoting heat tolerance of scleractinian coral Pocillopora damicornis

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ENVIRONMENTAL RESEARCH 2021年 195卷 110782页

作者： Yu, Xiaopeng Yu, Kefu Chen, Biao Liao, Zhiheng Qin, Zhenjun Yao, Qiucui Huang, Yanhua Liang, Jiayuan Huang, Wen Guangxi Univ Coral Reef Res Ctr China Sch Marine Sci Guangxi Lab Study Coral Reefs South China Sea Nanning Peoples R China Southern Marine Sci & Engn Guangdong Lab Zhuhai Peoples R China

Some scleractinian corals exhibit high thermal adaptability to climate changes, although the mechanism of their adaptation is unclear. This study investigated the adaptability of scleractinian coral Pocillopora damicornis to thermally variable reef environments by applying a nanopore-based rna sequencing method to characterize different transcription responses that promote heat tolerance of P. damicornis. We identified 1414 novel genes and optimized 6256 mis-annotated loci. Based on full-length transcriptome data, we identified complex alternative polyadenylation and alternative splicing events, which can improve our understanding of the genome annotation and gene structures of P. damicornis. Furthermore, we constructed differentially expressed lncrna-mrna co-expression networks, which may play a crucial role in the P. damicornis thermal adaptive response. KEGG function enrichment analysis revealed that P. damicornis from the high-temperature pool had a lower metabolic rate than that from the low-temperature pool. We hypothesize that metabolic readjustment, in the form of a lower metabolic rate, positively correlated with increased heat tolerance in P. damicornis in thermally variable reef environments. Our study provides novel insights into lncrnas that promote thermally tolerance of scleractinian corals in the thermally variable reef environment, suggesting potential mechanisms for their adaptation to global warming in the future.

关键词： Scleractinian coral Global warming Adaptation Nanopore-based rna sequencing non-coding rna

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Melatonin Increases the Sensitivity of Osteosarcoma Cells to Chemotherapy Drug Cisplatin

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DRUG RESEARCH 2022年第6期72卷 312-318页

作者： Hosseini, Foroogh Shanehbandi, Dariush Soleimanpour, Jafar Yousefi, Bahman Alemi, Forough Tabriz Univ Med Sci Fac Med Dept Biochem & Clin Labs Tabriz Iran Tabriz Univ Med Sci Mol Med Res Ctr Tabriz Iran Tabriz Univ Med Sci Shohada Teaching Hosp Dept Orthoped Surg Tabriz Iran

Chemotherapy, which is one of the common treatments for osteosarcoma (OS), has many side effects and in some cases has low effectiveness due to chemoresistance, hence it is vital to study new therapies for OS. In this regard, we combined melatonin with cisplatin and evaluate their effect on MG63 OS cells. Since melatonin has anti-cancer properties, we hypothesized that its combination with cisplatin could increase the effectiveness of cisplatin. Firstly, MTT assay was used to evaluate the cell viability and cytotoxicity of cisplatin on MG63 cells and the results showed that melatonin in combination with cisplatin increases the sensitivity of MG63 cells to cisplatin. In addition, qRT-PCR results showed that the expressions of miR-181 and P53, CYLD, CBX7 and BCL2 genes change in MG63 cells after treatment with the combination of cisplatin and melatonin, so that the expression of P53, CYLD and CBX7 increased and the expression of BCL2 and miR-181b decreases significantly. Furthermore, analysis of Annexin V/FITC assay data revealed that the rate of apoptosis in MG63 OS cell line remarkably promoted after treated with cisplatin and melatonin combination. As a result, our findings show that melatonin in combination with cisplatin increases the effectiveness of cisplatin in osteosarcoma cells and this study provides a newthera-peutic approach for OS.

关键词： Bone cancer cisplatin combination therapy P53 BCL2 non-coding rna

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Circrna-based AntimiR therapy: A novel approach to hypertension treatment

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non-coding rna RESEARCH 2025年 13卷 94-108页

作者： Tarhriz, Vahideh Hosseini, Kamran Abkhooie, Leila Lazartigues, Eric Louisiana State Univ Hlth Sci Ctr Cardiovasc Ctr Excellence New Orleans LA 70112 USA Southeast Louisiana Vet Healthcare Syst New Orleans LA 70119 USA Shiraz Univ Med Sci Shiraz Neurosci Res Ctr Shiraz Iran Lorestan Univ Med Sci Razi Herbal Med Res Ctr Khorramabad Iran Lorestan Univ Med Sci Sch Med Dept Med Biotechnol Khorramabad Iran

The increasing recognition of the types and functions of non-coding rnas has opened new avenues for their use as novel therapeutic strategies in the treatment of chronic diseases such as hypertension. While most preclinical and clinical studies on hypertension focus on prognosis and treatment, there are still no specific therapeutic approaches for primary and essential hypertension. Modest efficacy and reduced long-term adherence to treatment underscore the need for novel, mechanism-based strategies to address the underlying molecular mechanisms. AntimiRs, as synthetic rna molecules, and circular rnas (circrnas), as naturally occurring rna species that function as microrna sponges, could play a crucial role in regulating the renin-angiotensin system (RAS). These non-coding rnas hold significant potential as innovative approaches for managing primary and essential hypertension. This review aims to provide a comprehensive overview of circrna-mirna interactions involved in hypertension regulation via modulation of the RAS, their mechanisms of action, therapeutic advantages, and the major translational challenges, including delivery efficiency, off-target effects, and safety concerns. Optimization of the delivery systems, validating long-term efficacy, and navigating regulatory pathways to bring these promising ncrna-based therapies closer to preclinical and clinical research of antimiR-based therapies are addressed. Furthermore, this review highlights the potential of these new rna targets to fill the current therapeutic void and contribute to the advancement of precision medicine in hypertension and related cardiovascular diseases treatment.

关键词： non-coding rna circrnas AntimiRs Hypertension

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Effects of non-coding rnas in Prostate Cancer: Diagnosis, Prognosis, and Therapy

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BRATISLAVA MEDICAL JOUrnaL 2025年 1-19页

作者： Novakova, Zuzana Varchulova Milosovicova, Lubica Bernatova, Sona Neuschlova, Lucia Harsanyi, Stefan Comenius Univ Inst Med Biol Genet & Clin Genet Fac Med Sasinkova 4 Bratislava 81108 Slovakia

Prostate cancer remains the most commonly diagnosed malignancy in men worldwide, representing a major health challenge due to its heterogeneity, aggressive progression, and resistance to conventional therapies. Although improvements in diagnostic imaging, PSA screening, and targeted therapies have advanced clinical management, prostate cancer still presents substantial clinical challenges, notably progression to castration-resistant prostate cancer (CRPC) and metastatic disease. Recent research emphasizes the importance of non-coding rnas (ncrnas), including micrornas, small interfering rnas, PIWI-interacting rnas, small nucleolar rnas, small nuclear rnas, transfer rna-derived small rnas, Yrnas, vault rnas, circular rnas, and long non-coding rnas, in the regulation of gene expression, signaling pathways, tumor growth, metastasis, and therapy resistance. This review comprehensively synthesizes the current understanding of ncrnas in prostate cancer, highlighting their diverse regulatory functions, interactions, clinical implications, and potential as biomarkers and therapeutic targets. By integrating existing knowledge and exploring novel molecular mechanisms, we aim to facilitate the way to personalized prostate cancer management, stratification of patient risk, and precision therapeutic strategies.

关键词： Prostate cancer non-coding rna microrna circrna lncrna

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Prognostic Value of Lncrna KRT18P55 in Patients with Intestinal Type of Gastric Cancer

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JOUrnaL OF GASTROINTESTINAL CANCER 2022年第4期53卷 1014-1019页

作者： Tayefeh-Gholami, Samaneh Ghanbari, Mohammad Aghazadeh, Aida Rajabi, Ali Saber, Ali Hussen, Bashdar Mahmud Farsad-Akhtar, Nader Safaralizadeh, Reza Univ Tabriz Fac Nat Sci Dept Anim Biol Tabriz Iran Zimagene Med Genet Lab Avicenna St Hamadan Hamadan Iran Hawler Med Univ Coll Pharm Dept Pharmacognocy Erbil Iraq Univ Tabriz Fac Nat Sci Dept Plant Biol Tabriz Iran

Purpose Gastric cancer (GC) is a heterogeneous disease, and this heterogeneity significantly affects survival and treatment outcomes. Identification of molecular biomarkers specific for early-stage GC can help clinicians to choose more precise and effective treatment approaches. Long non-coding rnas (lncrnas) have the potential to be used as biomarkers because of their tissue specificity, stability, and availability in body fluids. In this study, we aimed to investigate changes in the expression levels of lncrna KRT18P55 and to assess its biomarker potentials in patients with GC. Methods Tumor and non-tumor marginal tissues were collected from 102 patients at Noor-Nejat Hospital (Tabriz, Iran). rna was isolated, and quantitative reverse transcriptase PCR (qRT-PCR) was performed to assess KRT18P55 expression levels in tumor and non-tumor tissue samples. The receiver operating characteristic (ROC) curve analysis was performed to evaluate potentials of KRT18P55 as a prognostic biomarker in GC. SPSS and GraphPad Prism software were used for data analysis. Results We found that KRT18P55 is significantly overexpressed in tumor as compared to non-tumor tissues (p < 0.0001). We found a significant association between KRT18P55 overexpression and intestinal GC subtype (p < 0.0001), lymph node metastasis (p = 0.013), and Helicobacter pylori infection (p = 0.033). Based on the ROC analysis, KRT18P55 showed a sensitivity and specificity of 53.92% and 77.45%, respectively. Conclusion Overexpression of KRT18P55 in gastric tumors is suggestive of its oncogenic role in GC. In addition, KRT18P55 may be used as a potential prognosis biomarker and therapeutic target in intestinal GC subtype.

关键词： non-coding rna Lncrna Biomarker Gastric cancer H pylori

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Functional divergence of Lncrnas in wheat-fungal interactions: insights from stem rust-responsive wheat transcriptomes

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PHYSIOLOGY AND MOLECULAR BIOLOGY OF PLANTS 2025年第5期31卷 709-727页

作者： Jyothsna, S. Nair, Minu M. Alagu, Manickavelu Cent Univ Kerala Dept Genom Sci Tejaswini Hills Kasaragod 671320 Kerala India

Stem rust of wheat, caused by the fungal pathogen Puccinia graminis f. sp. tritici (Pgt), is an economically significant disease affecting wheat production globally. The recent progress in high-throughput sequencing technology has uncovered the crucial role of non-coding rnas, an emerging yet influential regulatory genetic element modulating plant response against abiotic and biotic stresses. Long non-coding rnas (lncrnas) and micrornas (mirnas) are prominent regulatory nrnas, renowned for their ability to finely tune plant gene expression across transcriptional, post-transcriptional, and epigenetic layers. The current study adopts a comprehensive transcriptome sequencing approach to identify stem rust-responsive lncrnas from near isogenic lines of wheat introgressed with resistance gene Sr36, along with their susceptible variety, HD2329. A meticulous lncrna selection criterion yielded a total of 948 Pgt-responsive lncrnas. The detection of 11 lncrnas acting as mirna precursors, along with 590 mirna-lncrna target interactions further highlights the dynamic interplay between mirnas and lncrnas during Pgt infection in wheat. Moreover, the functional annotation of lncrna targets unveiled the prevalence of genes such as LRR receptor-like serine/threonine-protein kinases, disease resistance protein RPM1-like, chitin elicitor receptor kinase, nudix hydrolases and NAC transcription factors, that are involved in discrete biological pathways crucial for plant stress responses. Detection of 37 SSR marker-bearing lncrnas along with the interaction of lncrnas with disease-associated transcription factors such as C2H2, ERF, GATA and Dof, further elevate the significance of the study. The study unveils potential functional divergence within lncrnas and serves as a fine resource that can be harnessed to elucidate the interplay of coding and non-coding rnas governing wheat-fungal interactions.

关键词： Wheat stem rust Puccinia graminis f. sp. tritici Sr gene Transcriptomics non-coding rna lncrna

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Targeting riboswitches with synthetic small rnas for metabolic engineering

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METABOLIC ENGINEERING 2021年 68卷 59-67页

作者： Lins, Milca Rachel da Costa Ribeiro Amorim, Laura Araujo da Silva Correa, Graciely Gomes Picao, Bruno Willian Mack, Matthias Cerri, Marcel Otavio Pedrolli, Danielle Biscaro Univ Estadual Paulista UNESP Sch Pharmaceut Sci Dept Bioproc Engn & Biotechnol Rodovia Araraquara Jau Km 1 BR-14800903 Araraquara SP Brazil Mannheim Univ Appl Sci Inst Tech Microbiol Paul Wittsack Str 10 D-68163 Mannheim Germany

Our growing knowledge of the diversity of non-coding rnas in natural systems and our deepening knowledge of rna folding and function have fomented the rational design of rna regulators. Based on that knowledge, we designed and implemented a small rna tool to target bacterial riboswitches and activate gene expression (rtrna). The synthetic rtrna is suitable for regulation of gene expression both in cell-free and in cellular systems. It targets riboswitches to promote the antitermination folding regardless the cognate metabolite concentration. Therefore, it prevents transcription termination increasing gene expression up to 103-fold. We successfully used small rna arrays for multiplex targeting of riboswitches. Finally, we used the synthetic rtrnas to engineer an improved riboflavin producer strain. The easiness to design and construct, and the fact that the rtrna works as a single genome copy, make it an attractive tool for engineering industrial metabolite-producing strains.

关键词： Small rna non-coding rna Riboswitch Bacillus subtilis Synthetic biology Riboflavin

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Variation in the co-expression profile highlights a loss of mirna-mrna regulation in multiple cancer types

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non-coding rna RESEARCH 2022年第2期7卷 98-105页

作者： Pepe, Gerardo Parca, Luca Viviani, Lorenzo Ausiello, Gabriele Helmer-Citterich, Manuela Univ Roma Tor Vergata Dept Biol Rome Italy Italian Space Agcy Via Politecn Snc I-00133 Rome Italy

Recent research provides insight into the ability of mirna to regulate various pathways in several cancer types. Despite their involvement in the regulation of the mrna via targeting the 3'UTR, there are relatively few studies examining the changes in these regulatory mechanisms specific to single cancer types or shared between different cancer types. We analyzed samples where both mirna and mrna expression had been measured and performed a thorough correlation analysis on 7494 experimentally validated human mirna-mrna target-gene pairs in both healthy and tumoral samples. We show how more than 90% of these mirna-mrna interactions show a loss of regulation in the tumoral samples compared with their healthy counterparts. As expected, we found shared mirna-mrna dysregulated pairs among different tumors of the same tissue. However, anatomically different cancers also share multiple dysregulated interactions, suggesting that some cancer-related mechanisms are not tumor-specific. 2865 unique mirna-mrna pairs were identified across 13 cancer types, approximate to 40% of these pairs showed a loss of correlation in the tumoral samples in at least 2 out of the 13 analyzed cancers. Specifically, miR-200 family, miR-155 and miR-1 were identified, based on the computational analysis described below, as the mirnas that potentially lose the highest number of interactions across different samples (only literature-based interactions were used for this analysis). Moreover, the miR-34a/ALDH2 and miR-9/MTHFD2 pairs show a switch in their correlation between healthy and tumor kidney samples suggesting a possible change in the regulation exerted by the mirnas. Interestingly, the expression of these mrnas is also associated with the overall survival. The disruption of mirna regulation on its target, therefore, suggests the possible involvement of these pairs in cell malignant functions. The analysis reported here shows how the regulation of mirna-mrna interactions strongly differs betwee

关键词： Cancer non-coding rna mirna regulation Cancer biomarkers

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