Mao Wang, Weina Li, Guohui Han, Xiangdong Bai, Jun Xie
{"title":"MicroRNA-605-3p Inhibited the Growth and Chemoresistance of Osteosarcoma Cells via Negatively Modulating RAF1.","authors":"Mao Wang, Weina Li, Guohui Han, Xiangdong Bai, Jun Xie","doi":"10.2174/0109298665314658240712051206","DOIUrl":"10.2174/0109298665314658240712051206","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is the leading cancer-associated mortality in childhood and adolescence. Increasing evidence has demonstrated the key function of microRNAs (miRNAs) in OS development and chemoresistance. Among them, miRNA-605-3p acted as an important tumor suppressor and was frequently down-regulated in multiple cancers. However, the function of miR-650-3p in OS has not been reported.</p><p><strong>Objective: </strong>The aim of this work is to explore the novel role of miR-605-3p in osteosarcoma and its possible involvement in OS chemotherapy resistance.</p><p><strong>Methods: </strong>The expression levels of miR-605-3p in OS tissues and cells were assessed by reverse transcription quantitative PCR (RT-qPCR). The relevance of miR-605-3p with the prognosis of OS patients was determined by the Kaplan-Meier analysis. Additionally, the influence of miR-605-3p on OS cell growth was analyzed using the cell counting kit-8, colony formation assay, and flow cytometry. The mRNA and protein expression of RAF1 were detected by RT-qPCR and western blot. The binding of miR-605-3p with the 3'-UTR of RAF1 was confirmed by dual-luciferase reporter assay.</p><p><strong>Results: </strong>Our results showed that miR-605-3p was markedly decreased in OS tissues and cells. A lower level of miR-605-3p was strongly correlated with lymph node metastasis and poor 5-year overall survival rate of OS patients. <i>In vitro</i> assay found that miR-605-3p suppressed OS cell proliferation and promoted cell apoptosis. Mechanistically, the proto-oncogene RAF1 was seen as a target of miR-605-3p and strongly suppressed by miR-605-3p in OS cells. Restoration of RAF1 markedly eliminated the inhibitory effect of miR-605-3p on OS progression, suggesting RAF1 as a key mediator of miR-605-3p. Consistent with the decreased level of RAF1, miR-605-3p suppressed the activation of both MEK and ERK in OS cells, which are the targets of RAF1. Moreover, lower levels of miR-605-3p were found in chemoresistant OS patients, and downregulated miR-605-3p increased the resistance of OS cells to therapeutic agents.</p><p><strong>Conclusion: </strong>Our data revealed that miR-605-3p serves as a tumor suppressor gene by regulating RAF1 and increasing the chemosensitivity of OS cells, which provided the novel working mechanism of miR-605-3p in OS. Engineering stable nanovesicles that could efficiently deliver miR-605-3p with therapeutic activity into tumors could be a promising therapeutic approach for the treatment of OS.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"559-568"},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interleukin 6 Antagonists in Severe COVID-19 Disease: Cardiovascular and Respiratory Outcomes.","authors":"Shahzad Khan","doi":"10.2174/0109298665266730240118054023","DOIUrl":"10.2174/0109298665266730240118054023","url":null,"abstract":"<p><strong>Background: </strong>Inhibitors of interleukin 6 [IL-6] have been utilized to treat severe COVID-19 disease. Their immunosuppressive or immunomodulating impact may be beneficial in COVID-19.</p><p><strong>Objectives: </strong>To discuss the role of IL-6 inhibitors and assess various trials conducted to evaluate the efficacy of IL-6 inhibitors in COVID-19 disease.</p><p><strong>Summary: </strong>Two of the most common causes of mortality in COVID-19-infected critically ill individuals are acute respiratory distress syndrome (ARDS) and multiorgan failure. Increased levels of inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), is involved in the etiology of COVID-19. Most tissue damage, sepsis, and pulmonary and cardiovascular problems are caused mainly by the host defense system. Therefore, regulating this inflammatory cascade using immunomodulators is a prudent strategy. Although corticosteroids, as immunomodulators, are routinely used in COVID-19 management, interleukin (IL) inhibitors, especially IL-6 inhibitors, are also tested in many trials. Many studies have demonstrated that IL-6 inhibitors improve disease outcomes and decrease mortality, whereas others have shown that they are ineffective. In this paper, we briefly examined the role of IL-6 in COVID-19 pathogenesis and trials that support or refute the use of IL-6 inhibitors in treating COVID-19 disease.</p><p><strong>Results: </strong>Though mixed results are coming from trials regarding the adjuvant use of IL-6 inhibitors and standard anti-viral therapy with dexamethasone, a consensus favors using IL-6 inhibitors in severely ill COVID-19 patients regardless of the outcome.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"178-191"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuropeptide Network of Polycystic Ovary Syndrome - A Review.","authors":"Dheepthi Jayamurali, Nivetha Ravishankar, Nivedita Manoharan, Rajeshwari Parasuraman, Sri Kameshwaran Jayashankar, Sathya Narayanan Govindarajulu","doi":"10.2174/0109298665309949240822105900","DOIUrl":"10.2174/0109298665309949240822105900","url":null,"abstract":"<p><strong>Background: </strong>Polycystic Ovary Syndrome (PCOS), the ubiquitous reproductive disorder, has been documented as highly prevalent (6-9%) in India. 10% of women globally are predicted to have the disease. The highly mutable endocrinopathy, with differential clinical criteria for each diagnosis of PCOS, can mask the severity of the syndrome by influencing the incidence and occurrence of PCOS.</p><p><strong>Area covered: </strong>When there is a solid theoretical hypothesis between the neuroendocrine origin and ovarian origin of PCOS, recent evidence supports the neuroendocrine derivation of the pathology. It is considered of neuroendocrine basis - as it controls the ovarian axis and acts as a delicate target because it possesses receptors for various gonadal hormones, neurotransmitters & neuropeptides. Can these neuroendocrine alterations, variations in central brain circuits, and neuropeptide dysregulation be the tie that would link the pathophysiology of the disorder, the occurrence of all the 1˚ and 2˚ symptoms like polycystic ovaries, hyperandrogenism, obesity, insulin resistance, etc., in PCOS?</p><p><strong>Conclusion: </strong>This review anticipates providing a comprehensive overview of how neuropeptides such as Kisspeptin, Neurokinin B, Dynorphin A, β-Endorphin, Nesfatin, Neuropeptide Y, Phoenixin, Leptin, Ghrelin, Orexin, and Neudesin influence PCOS, the understanding of which may help to establish potential drug candidates against precise targets in these central circuits.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"667-680"},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tribute to Prof. Ben M. Dunn: A Remarkable Biochemist and Editor-in-Chief of Protein & Peptide Letters and Current Protein & Peptide Science.","authors":"","doi":"10.2174/092986653101240120233748","DOIUrl":"10.2174/092986653101240120233748","url":null,"abstract":"","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"31 1","pages":"1"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hua Ge, Yan Yan, Haomin Wang, Jun Bian, Zhilong Deng, Xian Su, Kaiyuan Luo, Jianfeng Bin
{"title":"Circular RNA hsa_circ_0005939 Regulates UHRF1BP1L Expression by Targeting miR-4693-3p to Promote Colorectal Cancer Progression.","authors":"Hua Ge, Yan Yan, Haomin Wang, Jun Bian, Zhilong Deng, Xian Su, Kaiyuan Luo, Jianfeng Bin","doi":"10.2174/0109298665297110240611115010","DOIUrl":"10.2174/0109298665297110240611115010","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) is the second most common and fatal cancer in China. circRNAs are different expressed between tumor and non-tumor tissues, and they are proved to be correlated with tumorigenesis and cancer progression.</p><p><strong>Objective: </strong>We aimed to explore the biological and molecular function of hsa_circ_0005939 in CRC.</p><p><strong>Methods: </strong>We collected and compared ten CRC tissues and four noncancerous tissues and performed circRNA sequencing. We investigated the hsa_circ_0005939 expression in fresh tissues from CRC and adjacent tissues by qPCR. Meanwhile, functional roles of hsa_circ_0005939 in CRC cells were explored by CCK-8, colony formation, wounding healing, cell apoptosis and western blot assays. RNA-FISH was used to confirm the cellular distribution of hsa_circ_0005939. Bioinformatic prediction and luciferase reporter assay were used to determine the mechanisms of hsa_circ_0005939.</p><p><strong>Results: </strong>Our results indicated that hsa_circ_0005939 was up-regulated in CRC tissues and cells. Up-regulation of hsa_circ_0005939 was associated with the occurrence and the number of lymph node metastasis of CRC. Hsa_circ_0005939 down-regulation inhibited cell proliferation, increased cell apoptosis and caused G2 phase arrest of CRC cells. Mechanistically, luciferase assay revealed that hsa_circ_0005939 acts as a molecular sponge for miR-4693-3p and then enhanced Ubiquitin Like With PHD And Ring Finger Domains 1 binding protein 1 like (UHRF1BP1L) expression.</p><p><strong>Conclusion: </strong>Our findings indicated an oncogenic role of hsa_circ_0005939 in CRC, and it enhanced malignant phenotypes of CRC cells through miR-4693-3p/UHRF1BP1L axis. Our study may offer promising biomarkers and therapeutic targets for CRC.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"437-446"},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Multifunction of TRIM26: From Immune Regulation to Oncology.","authors":"Jialai Zou, Kaiyi Niu, Tao Lu, Jianxun Kan, Hao Cheng, Lijian Xu","doi":"10.2174/0109298665311516240621114519","DOIUrl":"10.2174/0109298665311516240621114519","url":null,"abstract":"<p><p>Ubiquitination, a crucial post-translational modification, plays a role in nearly all physiological processes. Its functional execution depends on a series of catalytic reactions involving numerous proteases. TRIM26, a protein belonging to the TRIM family, exhibits E3 ubiquitin ligase activity because of its RING structural domain, and is present in diverse cell lineages. Over the last few decades, TRIM26 has been documented to engage in numerous physiological and pathological processes as a controller, demonstrating a diverse array of biological roles. Despite the growing research interest in TRIM26, there has been limited attention given to examining the protein's structure and function in existing reviews. This review begins with a concise overview of the composition and positioning of TRIM26 and then proceeds to examine its roles in immune response, viral invasion, and inflammatory processes. Simultaneously, we demonstrate the contribution of TRIM26 to the progression of various diseases, encompassing numerous malignancies and neurologic conditions. Finally, we have investigated the potential areas for future research on TRIM26.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"424-436"},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A R Satvik Iyengar, Prakash Y Khandave, Janek Bzdrenga, Florian Nachon, Xavier Brazzolotto, Abhay H Pande
{"title":"Warfare Nerve Agents and Paraoxonase-1 as a Potential Prophylactic Therapy against Intoxication.","authors":"A R Satvik Iyengar, Prakash Y Khandave, Janek Bzdrenga, Florian Nachon, Xavier Brazzolotto, Abhay H Pande","doi":"10.2174/0109298665284293240409045359","DOIUrl":"10.2174/0109298665284293240409045359","url":null,"abstract":"<p><p>Nerve agents are a class of lethal neurotoxic chemicals used in chemical warfare. In this review, we have discussed a brief history of chemical warfare, followed by an exploration of the historical context surrounding nerve agents. The article explores the classification of these agents, their contemporary uses, their toxicity mechanisms, and the disadvantages of the current treatment options for nerve agent poisoning. It then discusses the possible application of enzymes as prophylactics against nerve agent poisoning, outlining the benefits and drawbacks of paraoxonase- 1. Finally, the current studies on paraoxonase-1 are reviewed, highlighting that several challenges need to be addressed in the use of paraoxonase-1 in the actual field and that its potential as a prophylactic antidote against nerve agent poisoning needs to be evaluated. The literature used in this manuscript was searched using various electronic databases, such as PubMed, Google Scholar, Web of Science, Elsevier, Springer, ACS, Google Patent, and books using the keywords chemical warfare agent, butyrylcholinesterase, enzyme, nerve agent, prophylactic, and paraoxonase-1, with the time scale for the analysis of articles between 1960 to 2023. The study has suggested that concerted efforts by researchers and agencies must be made to develop effective countermeasures against NA poisoning and that paraoxonase-1 has suitable properties for the development of efficient prophylaxis against NA poisoning.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"345-355"},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to: Neuropeptide Network of Polycystic Ovary Syndrome - A Review.","authors":"Dheepthi Jayamurali, Nivetha Ravishankar, Nivedita Manoharan, Rajeshwari Parasuraman, Sri Kameshwaran Jayashankar, Sathya Narayanan Govindarajulu","doi":"10.2174/092986653111241230222032","DOIUrl":"https://doi.org/10.2174/092986653111241230222032","url":null,"abstract":"<p><p>An error was found in the affiliations of the author in the article titled 'Neuropeptide Network of Polycystic Ovary Syndrome - A Review'', published in Protein and Peptide Letters, 2024, 31(9), 667-680 [1]. Details of the error and a correction are provided here. Original: *Address correspondence Department of Physiology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600 113, India; E-mail: drgsathyanarayanan@gmail.com Corrected: *Address correspondence to this author at the Department of Physiology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600 113, India; E-mail: drgsathyanarayanan@gmail.com We regret the error and apologize to readers. The original article can be found online at: http://dx.doi.org/10.2174/0109298665309949240822105900 PMID: 39313871.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"31 11","pages":"907"},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent Trends in Development of Novel Therapeutics for Modulation of 14-3-3 Protein-Protein Interactions in Diseases.","authors":"Arshia Nazir","doi":"10.2174/0109298665330728241025082011","DOIUrl":"10.2174/0109298665330728241025082011","url":null,"abstract":"<p><p>14-3-3s constitute a group of proteins belonging to the phosphoserine/phosphothreonine family that are involved in the regulation of several physiological pathways by interacting with several client proteins. All the eukaryotic cells are known to possess 14-3-3 isoforms. In addition, 14-3-3s isolated from different eukaryotic cells share high sequence homology with each other. Seven isoforms (β, γ, ε, η, ζ, σ, and τ/θ) have been yet identified in mammals. These proteins participate in several physiological processes by either stimulating or interfering with the enzymatic activities of binding partners. These proteins take part in several human diseases upon dysregulation which include cancer and neurodegenerative disorders. Recently, a number of evidences suggest that the interaction of 14-3-3s with either oncogenic or pro-apoptotic proteins can lead to cancer development in animals. In the case of neurodegenerative disorders, 14-3-3s interact with Lewy bodies and neurofibrillary tangles in Parkinson's and Alzheimer's diseases, respectively. The current review focuses on strategies to regulate 14-3-3s' proteins in diseases. Potential strategies to regulate 14-3-3 interactions in disease conditions include the use of small interfering RNAs (siRNA), microRNA (miRNA), and modifications of 14-3-3s or their client proteins. In addition, some peptides or chemicals can also serve as potential inhibitors of 14-3-3. However, optimization of these therapeutic strategies is required for their practical implementations.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"850-861"},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Macromolecular Polymer Based Complexes: A Diverse Strategy for the Delivery of Nucleotides.","authors":"Dilpreet Singh","doi":"10.2174/0109298665310091240809103048","DOIUrl":"10.2174/0109298665310091240809103048","url":null,"abstract":"<p><p>This review explores the burgeoning field of macromolecular polymer-based complexes, highlighting their revolutionary potential for the delivery of nucleotides for therapeutic applications. These complexes, ingeniously crafted from a variety of polymers, offer a unique solution to the challenges of nucleotide delivery, including protection from degradation, targeted delivery, and controlled release. The focus of this report is primarily on the design principles, encapsulation strategies, and biological interactions of these complexes, with an emphasis on their biocompatibility, biodegradability, and ability to form diverse structures, such as nanoparticles and micelles. Significant attention is paid to the latest advancements in polymer science that enable the precise tailoring of these complexes for specific nucleotides, such as DNA, RNA, and siRNA. The review discusses the critical role of surface modifications and the incorporation of targeting ligands in enhancing cellular uptake and ensuring delivery to specific tissues or cells, thereby reducing off-target effects and improving therapeutic efficacy. Clinical applications of these polymer-based delivery systems are thoroughly examined with a focus on their use in treating genetic disorders, cancer, and infectious diseases. The review also addresses the challenges and limitations currently faced in this field, such as scalability, manufacturing complexities, and regulatory hurdles. Overall, this review provides a comprehensive overview of the current state and future prospects of macromolecular polymer-based complexes in nucleotide delivery. It underscores the significance of these systems in advancing the field of targeted therapeutics and their potential to reshape the landscape of medical treatment for a wide range of diseases.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"586-601"},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}