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Micrornas-mediated regulation of the differentiation of dental pulp-derived mesenchymal stem cells: a systematic review and bioinformatic analysis

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STEM CELL RESEARCH & THERAPY 2023年第1期14卷 1页

作者： Iranmanesh, Pedram Vedaei, Amirhossein Salehi-Mazandarani, Sadra Nikpour, Parvaneh Khazaei, Saber Khademi, Abbasali Galler, Kerstin M. M. Nekoofar, Mohammad-Hossein Dummer, Paul M. H. Isfahan Univ Med Sci Dent Res Inst Dent Res Ctr Dept EndodontSch Dent Esfahan Iran Isfahan Univ Med Sci Student Res Comm Sch Dent Esfahan Iran Isfahan Univ Med Sci Fac Med Dept Genet & Mol Biol Esfahan Iran Kermanshah Univ Med Sci Sch Dent Dept Endodont Kermanshah Iran Univ Hosp Erlangen Dept Conservat Dent & Periodontol Erlangen Germany Univ Tehran Med Sci Sch Dent Dept Endodont Tehran Iran Cardiff Univ Coll Biomed & Life Sci Sch Dent Cardiff Wales Univ Tehran Med Sci Sch Adv Technol Med Dept Tissue Engn Tehran Iran Bahcesehir Univ Sch Dent Dept Endodont Istanbul Turkiye

BackgroundHuman dental pulp-derived mesenchymal stem cells (hDP-MSCs), which include human dental pulp stem cells (hDPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs), are promising cell sources for regenerative therapies. Nevertheless, a lack of knowledge relating to the mechanisms regulating their differentiation has limited their clinical application. micrornas (mirnas) are important regulatory molecules in cellular processes including cell differentiation. This systematic review aims to provide a panel of mirnas that regulate the differentiation of hDP-MSCs including hDPSCs and SHEDs. Additionally, bioinformatic analyses were conducted to discover target genes, signaling pathways and gene ontologies associated with the identified *** literature search was performed in MEDLINE (via PubMed), Web of Science, Scopus, Embase and Cochrane Library. Experimental studies assessing the promotive/suppressive effect of mirnas on the differentiation of hDP-MSCs and studies evaluating changes to the expression of mirnas during the differentiation of hDP-MSCs were included. mirnas involved in odontogenic/osteogenic differentiation were then included in a bioinformatic analysis. A mirna-mrna network was constructed, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. A protein-protein interaction (PPI) network was also *** 766 initially identified records through database searching, 42 and 36 studies were included in qualitative synthesis and bioinformatic analyses, respectively. Thirteen mirnas promoted and 17 suppressed odontogenic/osteogenic differentiation of hDP-MSCs. hsa-miR-140-5p, hsa-miR-218 and hsa-miR-143 were more frequently reported suppressing the odontogenic/osteogenic differentiation of hDP-MSCs. hsa-miR-221 and hsa-miR-124 promoted and hsa-miR-140-5p inhibited neuronal differentiation, hsa-miR-26a-5p promoted and hsa-miR-424 suppressed angiogenic differentiation, an

关键词： Dental pulp Differentiation Microrna noncoding rna Regeneration Regenerative medicine Stem cell

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Epigenetics-based diagnostic and therapeutic strategies: shifting the paradigm in prostate cancer

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EPIGENOMICS 2023年第2期15卷 75-87页

作者： Clermont, Pier-Luc Univ Laval Quebec City PQ Afghanistan

Despite recent advances, prostate cancer (PCa) remains a leading cause of cancer morbidity and mortality. Clinically, PCa screening methods display low sensitivity and specificity, leading to suboptimal patient care. Recent research suggests that PCa progression is regulated by a coordinated spectrum of epigenetic alterations that notably involves noncoding rnas. These molecular aberrations drive PCa progression by inducing gene expression programs that promote metastatic dissemination. Epigenetic proteins and noncoding rnas can be detected noninvasively in body fluids, allowing improved PCa screening and prognosis. In addition, epigenetic alterations can be targeted pharmacologically, providing unprecedented therapeutic opportunities. This work reviews the current literature linking epigenetic dysregulation and PCa progression and proposes a framework for integrating epigenetic strategies into the clinical management of PCa.

关键词： CBX2 epigenetics EZH2 liquid biopsy noncoding rna prostate cancer therapeutics

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Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics

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CANCER CELL INTErnaTIONAL 2023年第1期23卷 238-238页

作者： Tabnak, Peyman Hasanzade Bashkandi, Aysa Ebrahimnezhad, Mohammad Soleimani, Mahdieh Tabriz Univ Med Sci Fac Med Tabriz Iran Tabriz Univ Med Sci Imam Reza Hosp Tabriz Iran Urmia Univ Med Sci Fac Med Orumiyeh Iran

Glioma is the most aggressive and malignant type of primary brain tumor, comprises the majority of central nervous system deaths, and is categorized into different subgroups according to its histological characteristics, including astrocytomas, oligodendrogliomas, glioblastoma multiforme (GBM), and mixed tumors. The forkhead box (FOX) transcription factors comprise a collection of proteins that play various roles in numerous complex molecular cascades and have been discovered to be differentially expressed in distinct glioma subtypes. FOXM1 and FOXOs have been recognized as crucial transcription factors in tumor cells, including glioma cells. Accumulating data indicates that FOXM1 acts as an oncogene in various types of cancers, and a significant part of studies has investigated its function in glioma. Although recent studies considered FOXO subgroups as tumor suppressors, there are pieces of evidence that they may have an oncogenic role. This review will discuss the subtle functions of FOXOs and FOXM1 in gliomas, dissecting their regulatory network with other proteins, micrornas and their role in glioma progression, including stem cell differentiation and therapy resistance/sensitivity, alongside highlighting recent pharmacological progress for modulating their expression.

关键词： Transcription factors Glioma Forkhead box protein M1 Forkhead box protein O1 Forkhead box protein O3 noncoding rna

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Nondomain biopolymers: Flexible molecular strategies to acquire biological functions

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GENES TO CELLS 2023年第8期28卷 539-552页

作者： Arakawa, Kazuharu Hirose, Tetsuro Inada, Toshifumi Ito, Takuhiro Kai, Toshie Oyama, Masaaki Tomari, Yukihide Yoda, Takao Nakagawa, Shinichi Keio Univ Inst Adv Biosci Tokyo Japan Osaka Univ Grad Sch Frontier Biosci RNA Biofunct Lab Suita Japan Univ Tokyo Inst Med Sci Div RNA & Gene Regulat Tokyo Japan RIKEN Ctr Biosyst Dynam Res Lab Translat Struct Biol Yokohama Japan Osaka Univ Grad Sch Frontier Biosci Germline Biol Lab Osaka Japan Univ Tokyo Inst Med Sci Med Prote Lab Tokyo Japan Univ Tokyo Inst Quantitat Biosci Lab RNA Funct Tokyo Japan Nagahama Inst Biosci & Technol Nagahama Japan Hokkaido Univ Fac Pharmaceut Sci RNA Biol Lab Sapporo Japan Hokkaido Univ Fac Pharmaceut Sci RNA Biol Lab Kita 12 Jo Nishi 6 ChomeKita Ku Sapporo 0600812 Japan

A long-standing assumption in molecular biology posits that the conservation of protein and nucleic acid sequences emphasizes the functional significance of biomolecules. These conserved sequences fold into distinct secondary and tertiary structures, enable highly specific molecular interactions, and regulate complex yet organized molecular processes within living cells. However, recent evidence suggests that biomolecules can also function through primary sequence regions that lack conservation across species or gene families. These regions typically do not form rigid structures, and their inherent flexibility is critical for their functional roles. This review examines the emerging roles and molecular mechanisms of "nondomain biomolecules," whose functions are not easily predicted due to the absence of conserved functional domains. We propose the hypothesis that both domain- and nondomain-type molecules work together to enable flexible and efficient molecular processes within the highly crowded intracellular environment.

关键词： intrinsically disordered proteins noncoding rna nondomain biopolymers nonmembranous organelles nuclear bodies phase separation

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Therapeutic potentials of natural products for post-traumatic stress disorder:A focus on epigenetics

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Chinese Herbal Medicines 2025年第2期17卷 203-219页

作者： Meijing Xu Minghui Cui Yu Wang Boru Li Lijin Feng Hang Xing Kuo Zhang Department of Pharmacology Shenyang Pharmaceutical UniversityShenyang 110016China

Post-traumatic stress disorder(PTSD)is a relatively common but complex mental illness with a range of diverse risk *** symptoms include the re-experience or avoidance of traumatic events,cognitive impairment,and *** the exact pathogenesis of PTSD is unclear,many studies indicate that epigenetic regulation plays a key role in its ***,numerous studies have indicated that the levels of histone acetylation and methylation,DNA methylation,and noncoding rna are altered in PTSD *** to this,natural products have been found to achieve epigenetic regulation of PTSD by regulating the expression of epigenetic enzymes,long noncoding rna(lncrna),and mirna,thereby playing a role in improving PTSD *** date,however,no epigenetic regulation related drugs have been used in the treatment of ***,while natural products that can epigenetically regulate PTSD have received increasing levels of attention,there have not yet been any systematic reports on the ***,we summarized the roles and mechanisms of natural products in the epigenetic regulation of PTSD,providing a novel and unique perspective that will help to guide the development and application of new PTSD treatments.

关键词： DNA methylation epigenetic regulation histone modification natural products noncoding rna post-traumatic stress disorder

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SNORD60 promotes the tumorigenesis and progression of endometrial cancer through binding PIK3CA and regulating PI3K/AKT/mTOR signaling pathway

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MOLECULAR CARCINOGENESIS 2023年第4期62卷 413-426页

作者： Wu, Wu Chen, Xi Liu, Xin Bao, Hai-juan Li, Qian-hui Xian, Jing-yuan Lu, Bing-feng Zhao, Yang Chen, Shuo Guangzhou Med Univ Affiliated Hosp 3 Dept Gynecol Oncol Res Off Guangdong Prov Key Lab Major Obstet DisDept Obst 63 Duobao Rd Guangzhou 510150 Guangdong Peoples R China

Endometrial carcinoma is a common gynecological malignant tumor, small nucleolar rnas (snornas) are involved in cancer development. However, researches on the roles of snornas in endometrial carcinoma are limited. The expression levels of snornas in endometrial cancer tissues were analyzed using The Cancer Genome Atlas (TCGA) database. Antisense oligonucleotides (ASOs) and plasmids were used for transfection. Moreover, CCK-8, EdU, wound-healing assay, transwell, cell apoptosis, western blotting, and xenograft model were employed to examine the biological functions of related molecules. real-time reverse transcription polymerase chain reaction and western blotting were performed to detect messenger rna (mrna) and protein levels. Including bioinformatics, fluorescence in situ hybridization, rna pulldown, actinomycin D and RTL-P assays were also carried out to explore the molecular mechanism. Analysis of data from TCGA showed that the expression level of small nucleolar rna, C/D box 60 (SNORD60) in endometrial cancer tissues is observably higher than that in normal endometrial tissues. Further research suggested that SNORD60 played a carcinogenic role both in vitro and in vivo, and significantly upregulated the expression of PIK3CA. However, the carcinogenic effects can be reversed by knocking down fibrillarin (FBL) or PIK3CA. SNORD60 forms complexes by binding with 2 & PRIME;-O-methyltransferase fibrillarin, thus catalyzes the 2 & PRIME;-O-methylation (Nm) modification of PIK3CA mrna and modulates the PI3K/AKT/mTOR signaling pathway, so as to promote the development of endometrial cancer. In short, SNORD60 might become a new biomarker for the therapy of endometrial cancer in the future and provide new strategies for diagnosis and treatment.

关键词： 2'-O-methylation endometrial carcinoma noncoding rna PIK3CA snornas

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Circrna hsa_circ_0000043 acts as a miR-4492 sponge to promote lung cancer progression via BDNF and STAT3 expression regulation in anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide-transformed 16HBE cells

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TOXICOLOGICAL SCIENCES 2023年第1期195卷 87-102页

作者： Liu, Jiayu Xie, Jiaying Xu, Enwu Xu, Binhe Zhou, Jiaxin Zhou, Jiazhen Yang, Qiaoyuan Guangzhou Med Univ Inst Chem Carcinogenesis Sch Publ Hlth Guangzhou 511436 Peoples R China Gen Hosp Southern Theater Command PLA Dept Thorac Surg Guangzhou 510010 Peoples R China Zunyi Med Univ Basic Med Coll Zunyi 563000 Peoples R China Guangzhou Med Univ Inst Chem Carcinogenesis Xinzao TownPanyu Dist Guangzhou 511436 Peoples R China

Increasing evidence shows that circular rna (circrna) plays an important role in the progression of lung cancer. In this study, we found that has_circ_0000043 was highly expressed in 16HBE-T human bronchial epithelial cells that were malignantly transformed by benzo[a]pyrene-trans-7,8-diol-9,10-epoxide via circrna microarray. We verified that hsa_circ_0000043 was also significantly overexpressed in lung cancer cell lines and tissues. Moreover, hsa_circ_0000043 overexpression was positively correlated with poor clinicopathological parameters, such as tumor-node metastasis stage, distant metastasis, lymph-node metastasis, and overall survival. In vitro assays revealed that hsa_circ_0000043 inhibition suppressed 16HBE-T cell proliferation, migration, and invasion. Furthermore, hsa_circ_0000043 inhibition suppressed tumor growth in a mouse xenograft model. We discovered that hsa_circ_0000043 binds with miR-4492, acting as a miR-4492 sponge. Decreased miR-4492 expression was also associated with poor clinicopathological parameters. Thus, hsa_circ_0000043 was shown to contribute to the proliferation, malignant transformation ability, migration, and invasion of 16HBE-T cells via miR-4492 sponging and BDNF and STAT3 involvement.

关键词： lung cancer circrna hsa_circ_0000043 noncoding rna miR-4492

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Propofol-Induced Developmental Neurotoxicity: From Mechanisms to Therapeutic Strategies

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ACS CHEMICAL NEUROSCIENCE 2023年第6期14卷 1017-1032页

作者： Li, Yu Zhang, Jing Qingdao Univ Dept Anesthesiol Affiliated Hosp Qingdao 266000 Peoples R China Qingdao Univ Dept Med Qingdao 266000 Peoples R China

Propofol is the most commonly used intravenous general anesthetic in clinical anesthesia, and it is also widely used in general anesthesia for pregnant women and infants. Some clinical and preclinical studies have found that propofol causes damage to the immature nervous system, which may lead to neurodevelopmental disorders and cognitive dysfunction in infants and children. However, its potential molecular mechanism has not been fully elucidated. Recent in vivo and in vitro studies have found that some exogenous drugs and interventions can effectively alleviate propofol-induced neurotoxicity. In this review, we focus on the relevant preclinical studies and summarize the latest findings on the potential mechanisms and therapeutic strategies of propofolinduced developmental neurotoxicity.

关键词： Propofol neurotoxicity autophagy mitochondria neurotrophin noncoding rna

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noncoding Ribonucleic Acids (rnas) May Improve Response to Immunotherapy in Pancreatic Cancer

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ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE 2024年第9期7卷 2557-2572页

作者： Ala, Moein Univ Tehran Med Sci Expt Med Res Ctr Tehran *** Iran

Pancreatic ductal adenocarcinoma (PDAC) is the seventh most common cause of cancer-related mortality. Despite different methods of treatment, nearly more than 90% of patients with PDAC die shortly after diagnosis. Contrary to promising results in other cancers, immune checkpoint inhibitors (ICIs) showed limited success in PDAC. Recent studies have shown that noncoding rnas (ncrnas) are extensively involved in PDAC cell-immune cell interaction and mediate immune evasion in this vicious cancer. PDAC cells recruit numerous ncrnas to widely affect the phenotype and function of immune cells through various mechanisms. For instance, PDAC cells upregulate miR-301a and downregulate miR-340 to induce M2 polarization of macrophages or overexpress miR-203, miR-146a, and miR-212-3p to downregulate toll-like receptor 4 (TLR4), CD80, CD86, CD1a, major histocompatibility complex (MHC) II, and CD83, thereby evading recognition by dendritic cells. By downregulating miR-4299 and miR-153, PDAC cells can decrease the expression of NK group 2D (NKG2D) and MHC class I chain-related molecules A and B (MICA/B) to blunt the natural killer (NK) cell response. PDAC cells also highly express lncrna AL137789.1, hsa_circ_0046523, lncrna LINC00460, and miR-155-5p to upregulate immune checkpoint proteins and escape T cell cytotoxicity. On the other hand, ncrnas derived from suppressive immune cells promote proliferation, invasion, and drug resistance in PDAC cells. ncrnas can be applied to overcome resistance to ICIs, monitor the immune microenvironment of PDAC, and predict response to ICIs. This Review article comprehensively discusses recent findings regarding the roles of ncrnas in the immune evasion of PDAC.

关键词： PDAC Immunotherapy Immune evasion noncoding rna Microrna Long noncoding rna Circular rna

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NMR Studies of Genomic rna in 3′ Untranslated Region Unveil Pseudoknot Structure that Initiates Viral rna Replication in SARS-CoV-2

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JACS AU 2024年第4期4卷 1323-1333页

作者： Ohyama, Takako Osawa, Takuo Sekine, Shun-ichi Ishii, Yoshitaka RIKEN Ctr Biosyst Dynam Res Lab Adv NMR Applicat & Dev Yokohama Kanagawa 2300045 Japan Tokyo Inst Technol Sch Life Sci & Technol Yokohama Kanagawa 2268503 Japan RIKEN Lab Transcript Struct Biol Ctr Biosyst Dynam Res Yokohama 2300045 Japan

In the 3 ' untranslated region of the SARS-CoV-2 virus rna genome, genomic rna replication is initiated in the highly conserved region called3 ' PK, containing three stem structures (P1pk, P2, and P5). According to one proposed mechanism, P1pk and distal P2 stems switch their structure to a pseudoknot through base-pairing, thereby initiating transcription by recruiting rna-dependent rna polymerase complexed with nonstructural proteins (nsp)7 and nsp8. However, experimental evidence of pseudoknot formation or structural switching is unavailable. Using SARS-CoV-2 3 ' PK fragments, we show that 3 ' PK adopted stem-loop and pseudoknot forms in a mutually exclusive manner. When P1pk and P2 formed a pseudoknot, the P5 stem, which includes a sequence at the 3 ' end, exited from the stem-loop structure and opened up. Interaction with the nsp7/nsp8 complex destabilized the stem-loop form but did not alter the pseudoknot form. These results suggest that the interaction between the pseudoknot and nsp7/nsp8 complex transformed the 3 ' end of viral genomic rna into single-stranded rna ready for synthesis, presenting the unique pseudoknot structure as a potential pharmacological target.

关键词： noncoding rna secondary structure SARS-CoV-2 NMR

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