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The functional role of circular rnas in the pathogenesis of retinoblastoma: a new potential biomarker and therapeutic target?

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CLINICAL & TRANSLATIONAL ONCOLOGY 2023年第8期25卷 2350-2364页

作者： Karami Fath, Mohsen Pourbagher Benam, Sasan Kouhi Esfahani, Niloofar Shahkarami, Negar Shafa, Shahriyar Bagheri, Hossein Shafagh, Seyyed-Ghavam Payandeh, Zahra Barati, Ghasem Kharazmi Univ Fac Biol Sci Dept Cellular & Mol Biol Tehran Iran Urmia Univ Med Sci Fac Med Orumiyeh Iran Rudn Univ Moscow Fac Med Moscow Russia Fasa Univ Med Sci Sch Allied Med Sci Fasa Iran Kerman Univ Med Sci Sch Med Kerman Iran Islamic Azad Univ Tehran Branch Fac Med Tehran Iran Iran Univ Med Sci Fac Med Tehran Iran Karolinska Inst Dept Med Biochem & Biophys Div Med Inflammat Res Stockholm Sweden Stem Cell Technol Res Ctr Tehran Iran

Retinoblastoma (RB) is a common cancer in infants and children. It is a curable disease;however, a delayed diagnosis or treatment makes the treatment difficult. Genetic mutations have a central role in the pathogenesis of RB. Genetic materials such as rnas (coding and non-coding rnas) are also involved in the progression of the tumor. Circular rna (circrna) is the most recently identified rna and is involved in regulating gene expression mainly through "microrna sponges". The dysregulation of circrnas has been observed in several diseases and tumors. Also, various studies have shown that circrnas expression is changed in RB tissues. Due to their role in the pathogenesis of the disease, circrnas might be helpful as a diagnostic or prognostic biomarker in patients with RB. In addition, circrnas could be a suitable therapeutic target to treat RB in a targeted therapy approach.

关键词： Retinoblastoma non-coding rna Circular rna Biomarker Cancer therapy

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The role of T cells in acute ischemic stroke

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BRAIN RESEARCH BULLETIN 2023年 196卷 20-33页

作者： Wang, Yi-Ran Cui, Wen-Qiang Wu, Hong-Yun Xu, Xiang-Dong Xu, Xiang-Qing Shandong Univ Tradit Chinese Med Coll Chinese Med Jinan Peoples R China Shandong Univ Tradit Chinese Med Affiliated Hosp Dept Neurol Jinan Peoples R China Shandong Univ Tradit Chinese Med Coll Clin Med 1 Jinan Peoples R China Shandong Univ Tradit Chinese Med Affiliated Hosp Expt Ctr Jinan Peoples R China

Acute ischemic stroke (AIS) is associated with high rates of disability and mortality, exerting a substantial impact on overall survival and health-related quality of life. Treatment of AIS remains challenging given that the underlying pathologic mechanisms remain unclear. However, recent research has demonstrated that the immune system plays a key role in the development of AIS. Numerous studies have reported infiltration of T cells into ischemic brain tissue. While some types of T cells can promote the development of inflammatory responses and aggravate ischemic damage in patients with AIS, other T cells appear to exert neuroprotective effects via immunosuppression and other mechanisms. In this review, we discuss the recent findings regarding the infiltration of T cells into ischemic brain tissue, and the mechanisms governing how T cells can facilitate tissue injury or neuroprotection in AIS. Factors influencing the function of T cells, such as intestinal microflora and sex differences, are also discussed. We also explore the recent research on the effect of non-coding rna on T cells after stroke, as well as the potential for specifically targeting T cells in the treatment of stroke patients.

关键词： Acute ischemic stroke T cell Immune response Neuroprotective effect Gut microbiome non-coding rna

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The role of lncrnas/mirnas/Sirt1 axis in myocardial and cerebral injury

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CELL CYCLE 2023年第9期22卷 1062-1073页

作者： Barangi, Samira Hayes, A. Wallace Karimi, Gholamreza Mashhad Univ Med Sci Pharmaceut Technol Inst Pharmaceut Res Ctr Mashhad Iran Michigan State Univ E Lansing MI USA Univ S Florida Tampa FL USA Mashhad Univ Med Sci Sch Pharm Dept Pharmacodynam & Toxicol Mashhad Iran Mashhad Univ Med Sci Sch Pharm Dept Pharmacodynam & Toxicol Pharmacol & Toxicol POB 1365-91775 Mashhad Iran

In recent years, researchers have begun to realize the importance of the role of non-coding rnas in the treatment of cancer and cardiovascular and neurological diseases. Lncrnas and mirnas are important non-coding rnas, which regulate gene expression and activate mrna translation through binding to diverse target sites. Their involvement in the regulation of protein function and the modulation of physiological and pathological conditions continues to be investigated. Sirtuins, especially Sirt1, have a critical function in regulating a variety of physiological processes such as oxidative stress, inflammation, apoptosis, and autophagy. The lncrnas/mirnas/Sirt1 axis may be a novel regulatory mechanism, which is involved in the progression and/or prevention of numerous diseases. This review focuses on recent findings on the crosstalk between non-coding rnas and Sirt1 in myocardial and cerebral injuries and may provide some insight into the development of novel approaches in the treatment of these disorders.

关键词： non-coding rna microrna MALAT1 ANRIL ischemia atherosclerosis

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The therapeutic potential of circular rna in triplenegative breast cancer

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Cancer Drug Resistance 2024年第1期7卷 855-868页

作者： Aiqi Xu Lewei Zhu Chengcai Yao Wen Zhou Ziyun Guan Department of Breast Oncology School of MedicineSouth China University of TechnologyGuangzhou 510006GuangdongChina Department of Breast Surgery The First People’s Hospital of FoshanFoshan 528000GuangdongChina The Sixth Affiliated Hospital School of MedicineSouth China University of TechnologyFoshan 528200GuangdongChina

Triple-negative breast cancer(TNBC)is among the most aggressive subtypes of the disease that does not express estrogen receptor,progesterone receptor,and human epidermal growth factor receptor *** rnas(circrnas)are a type of non-coding rna with a circular shape formed by non-standard splicing or reverse *** circrnas exhibit abnormal expression in various malignancies,showing their critical role in the emergence and growth of *** studies have shown evidence supporting the idea that certain circrnas regulate the proliferation and metastasis of *** addition,circrnas alter metabolism and the immune microenvironment to promote or inhibit the development of ***,circrnas may affect the efficacy of clinical drug therapy,serve as therapeutic targets,and be used as molecular biomarkers in the ***,we will first summarize the biogenesis and function of ***,we will explain current research on circrnas related to TNBC and their potential to serve as therapeutic targets or biomarkers for future drug development,providing a new direction and idea for TNBC therapy.

关键词： Triple-negative breast cancer circular rna non-coding rna

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Dietary flavonoids as modulators of non-coding rnas in hormone-associated cancer

Food Chemistry Advances

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Food Chemistry Advances 2023年 2卷

作者： Dey, Saurabh Biswas, Bini Ballav, Sangeeta Sahu, Vishal Kumar Ranjan, Amit Basu, Soumya Cancer and Translational Research Centre Dr. D Y Patil Biotechnology and Bioinformatics Institute Dr. D Y Patil Vidyapeeth Tathawade Pune 411033 India

non-coding rna (ncrnas) is greatly known to be involved in many cellular processes such as growth and development including tumorigenesis. Alterations in expression of ncrnas are observed in several cancers. Therefore, they are regarded as potential players in carcinogenesis. In a broader view, it has been documented that ncrnas are also involved in hormone-associated cancers (HACs) by regulating their epigenetic processes. Hence, HACs emerge on the radar of scientific community and cancer research as they are widely influenced by hormone levels and latter promotes cancer growth. Although various risk factors point to HACs, findings are inconsistent and not uniform. Dietary flavonoids are amongst the natural compounds that are capable of repressing the proliferation and growth of numerous cancer cells. This could be rewarding and might open new avenues for cancer treatment. In addition, flavonoids seem to have anti-hormone like properties in HACs. However, there are no direct assessment of flavonoids and their effects in HACs. The studies are not stringent enough to evaluate the intake of these dietary flavonoids. Herein, the present review highlights the role of numerous dietary flavonoids as ncrna modulators in HACs. Mechanisms of ncrna regulation and the role of hormones associated with hormone-specific cancer has also been discussed. © 2023 The Authors

关键词： Dietary flavonoid Epigenetic regulation Hormone-associated cancer Long non-coding rna Microrna non-coding rna

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Characterization of small nucleolar rna retaining transcripts in human normal and cancer cells

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non-coding rna Research 2025年 13卷 153-161页

作者： Rambaldelli, Guglielmo Asghar, Sidra Venturi, Giulia Zacchini, Federico Serra, Margherita Giovannini, Catia Gramantieri, Laura Bernini, Marco Inga, Alberto Dassi, Erik Montanaro, Lorenzo Department of Medical and Surgical Sciences (DIMEC) Bologna University Via Massarenti 9 Bologna 40138 Italy Departmental Program in Laboratory Medicine IRCCS Azienda Ospedaliero-Universitaria di Bologna Via Albertoni 15 Bologna 40138 Italy Unit of Breast Surgery IRCCS Azienda Ospedaliero-Universitaria di Bologna Via Albertoni 15 Bologna 40138 Italy Division of Internal Medicine Hepatobiliary and Immunoallergic Diseases IRCCS Azienda Ospedaliero-Universitaria di Bologna Via Albertoni 15 Bologna 40138 Italy Department of Cellular Computational and Integrative Biology (CIBIO) Trento University Via Sommarive 9 Povo (TN) 38123 Italy

Small nucleolar rnas are non-coding rnas typically encoded within the introns of both protein-coding and non-coding genes. Interestingly, a significant fraction of snorna sequences is found as retained introns of specific mrna isoforms expressed from their host gene. In the present study, we aimed to define the representation of small nucleolar rna retaining transcripts across various human cell types and tissues including cancer. We found that these type of transcripts are widely represented in normal tissues and cancer-derived cell lines, appearing both in their full-length form and, frequently, in a shorter variant. We characterized the shortening position, which occurs at or very close to the retained small nucleolar rna sequence at the 5′ end. Interestingly, for some transcripts this shorter variant represents the only form detected. In addition, some of the small nucleolar rna retaining transcripts can be localized into the cellular cytoplasmic fraction. Moreover, our findings point out that a variable but consistent proportion of small nucleolar rna sequences in cells, tissues, and liquid biopsy samples is, in fact, present as small nucleolar rna retaining transcripts, indicating that these elements should be carefully considered when snorna are evaluated as biomarkers. Considering that short reads and gene-based transcriptomic analysis completely overlooked these transcripts, potentially missing critical insights into their involvement in cancer and other diseases, our results strongly indicate that these type of transcripts should be further investigated in different contexts to better understand their biogenesis, sequence features, presence, and role within cells. © 2025 The Authors

关键词： Intron-retention Long-read transcriptomic analysis non-coding rna rna isoforms

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Evaluation of exo-long noncoding rna MALAT1 in OSCC in comparison to dysplastic and normal: A cross-sectional study

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Journal of Oral Biology and Craniofacial Research 2025年第1期15卷 123-128页

作者： Sekar, Ramya Jayaraman, Selvaraj Veeraraghavan, VishnuPriya Krishnamoorthy, Kalaiselvi Aramanai, Shubhra Chauhan Natarajan, Sathan Raj Centre of Molecular Medicine and Diagnostics (COMManD) Department of Biochemistry Saveetha Dental College and Hospitals Saveetha Institute of Medical and Technical Sciences Saveetha University Chennai 600077 India Department of Oral & Maxillofacial Pathology and Oral Microbiology Meenakshi Ammal Dental College and Hospital Meenakshi Academy of Higher Education and Research (Deemed to Be University) Chennai 600095 India Oral Oncology Unit Department of Oral and Maxillofacial Surgery Meenakshi Ammal Dental College and Hospital Meenakshi Academy of Higher Education and Research (Deemed to Be University) Chennai 600095 India

Objective: This study explores the role of MALAT1 as a valuable target for creating minimally-invasive diagnostic methods and personalized treatments in the management of OSCC. It focuses on evaluating the role of exosomal MALAT1 in the progression of dysplasia to OSCC by influencing the PI3K/AKT pathway. Method: This cross-sectional study evaluated MALAT1 expression and PI3K/AKT pathway components in exosomes derived from plasma samples of patients with various stages of oral dysplasia, OSCC and compared with normal. rna concentration was estimated, real-time polymerase chain reaction (qPCR) was used for quantitative analysis. Gene expression levels of MALAT1, PI3K, AKT1, and PTEN were analysed and compared across groups using one way ANOVA and Post-hoc Tukey analysis was performed for pairwise comparisons to assess correlations between MALAT1 expression and PI3K/AKT pathway components. Result: MALAT1 was found to be overexpressed in OSCC in comparison to normal, significantly (p < 0.001∗). There was no significant change in expression pattern of MALAT1 between dysplastic patients and normal, yet, significant association was found on corelation analysis between expression pattern of MALAT1 and PI3K/AKT/PTEN (p 0.001∗) among individuals of dysplasia and OSCC. As well pairwise comparisons of MALAT1 expression levels between all three stages of dysplasia showed significant association (p < 0.001∗). Conclusion: MALAT1 stands out as a key player in the complex landscape of OSCC pathogenesis, impacting tumorigenesis, metastasis, and treatment outcomes through multifaceted molecular mechanisms. Continued research into MALAT1's regulatory roles and its interactions within the tumor microenvironment holds promise for uncovering novel therapeutic targets and biomarkers that could redefine the management of OSCC in the future. © 2024 The Authors

关键词： Dysplasia Exosomes lncrna non-coding rna OSCC Tumor microenvironment

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Micrornas and lysosomal membrane proteins: Critical interactions in tumor progression and therapy

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BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER 2025年第3期1880卷 189303页

作者： Xu, Jiahao Liu, Shiqiang Jin, Yujie Wang, Lizhuo Gao, Jialin Wannan Med Coll Yijishan Hosp Affiliated Hosp 1 Dept Endocrinol & Genet Metab Wuhu Anhui Peoples R China Wannan Med Coll Yijishan Hosp Affiliated Hosp 1 Inst Endocrine & Metab Dis Wuhu Anhui Peoples R China Wannan Med Coll Anhui Prov Key Lab Basic Res & Transformat Age Rel Wuhu Anhui Peoples R China Wannan Med Collage Dept Biochem & Mol Biol Wuhu Anhui Peoples R China Wannan Med Coll Sch Clin Med Wuhu Peoples R China

Cancer development is influenced by genetic and epigenetic variations, with the interactions between micrornas (mirnas) and lysosomal membrane proteins (LMPs) representing key regulatory mechanisms with potential as therapeutic targets. This review focuses on the complex regulatory mechanisms of mirnas and LMPs in tumor progression, specifically highlighting their roles in tumor suppression, tumor promotion, tumor therapy, and drug resistance and their future application in treatment strategies. Overall, the interactions of LMPs with mirnas have critical roles in tumor regulation, and studies of these interactions will further highlight their molecular contributions to cancer development.

关键词： Microrna Lysosomal membrane protein Cancer Gene regulation non-coding rna

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β-Lactoglobulin affects the oxidative status and viability of equine endometrial progenitor cells via lncrna-mrna-mirna regulatory associations

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JOUrnaL OF CELLULAR AND MOLECULAR MEDICINE 2023年第7期27卷 927-938页

作者： Data, Krzysztof Marcinkowska, Klaudia Bus, Klaudia Valihrach, Lukas Pawlak, Edyta Smieszek, Agnieszka Univ Environm & Life Sci Fac Biol & Anim Sci Dept Expt Biol Wroclaw Poland Inst Biotechnol CAS Lab Gene Express Biocev Vestec Czech Republic Hirszfeld Inst Immunol & Expt Therapy Dept Expt Therapy Lab Immunopathol Wroclaw Poland Univ Environm & Life Sci Fac Biol & Anim Sci Dept Expt Biol PL-50375 Wroclaw Poland

The beta-lactoglobulin (beta-LG) was previously characterized as a mild antioxidant modulating cell viability. However, its biological action regarding endometrial stromal cell cytophysiology and function has never been considered. In this study, we investigated the influence of beta-LG on the cellular status of equine endometrial progenitor cells under oxidative stress. The study showed that beta-LG decreased the intracellular accumulation of reactive oxygen species, simultaneously ameliorating cell viability and exerting an anti-apoptotic effect. However, at the transcriptional level, the reduced mrna expression of pro-apoptotic factors (i.e. BAX and BAD) was accompanied by decreased expression of mrna for anti-apoptotic BCL-2 and genes coding antioxidant enzymes (CAT, SOD-1, GPx). Still, we have also noted the positive effect of beta-LG on the expression profile of transcripts involved in endometrial viability and receptivity, including ITGB1, ENPP3, TUNAR and miR-19b-3p. Finally, the expression of master factors of endometrial decidualization, namely prolactin and IGFBP1, was increased in response to beta-LG, while non-coding rnas (ncrnas), that is lncrna MALAT1 and miR-200b-3p, were upregulated. Our findings indicate a novel potential role of beta-LG as a molecule regulating endometrial tissue functionality, promoting viability and normalizing the oxidative status of endometrial progenitor cells. The possible mechanism of beta-LG action includes the activation of ncrnas essential for tissue regeneration, such as lncrna MALAT-1/TUNAR and miR-19b-3p/miR-200b-3p.

关键词： beta-lactoglobulin endometrium non-coding rna progenitor cells

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Time-resolved Small-rna Sequencing Identifies Micrornas Critical for Formation of Embryonic Stem Cells from the Inner Cell Mass of Mouse Embryos

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STEM CELL REVIEWS AND REPORTS 2023年第7期19卷 2361-2377页

作者： Moradi, Sharif Guenther, Stefan Soori, Samira Sharifi-Zarchi, Ali Kuenne, Carsten Khoddami, Vahid Tavakol, Pouya Kreutzer, Susanne Braun, Thomas Baharvand, Hossein ACECR Royan Inst Stem Cell Biol & Technol Cell Sci Res Ctr Dept Stem Cells & Dev Biol Tehran Iran Max Planck Inst Heart & Lung Res Dept Cardiac Dev & Remodelling Ludwigstr 43 D-61231 Bad Nauheim Germany Sharif Univ Technol Comp Engn Dept Tehran Iran Univ Sci & Culture Sch Basic Sci & Adv Technol Biol Dept Dev Biol Tehran Iran

Cells of the inner cell mass (ICM) acquire a unique ability for unlimited self-renewal during transition into embryonic stem cells (ESCs) in vitro, while preserving their natural multi-lineage differentiation potential. Several different pathways have been identified to play roles in ESC formation but the function of non-coding rnas in this process is poorly understood. Here, we describe several micrornas (mirnas) that are crucial for efficient generation of mouse ESCs from ICMs. Using small-rna sequencing, we characterize dynamic changes in mirna expression profiles during outgrowth of ICMs in a high-resolution, time-course dependent manner. We report several waves of mirna transcription during ESC formation, to which mirnas from the imprinted Dlk1-Dio3 locus contribute extensively. In silico analyses followed by functional investigations reveal that Dlk1-Dio3 locus-embedded mirnas (miR-541-5p, miR-410-3p, and miR-381-3p), miR-183-5p, and miR-302b-3p promote, while miR-212-5p and let-7d-3p inhibit ESC formation. Collectively, these findings offer new mechanistic insights into the role of mirnas during ESC derivation.

关键词： Blastocyst non-coding rna Pluripotency Microrna profiling ESC derivation Differentiation Stemness Ground-state pluripotency

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