Targets (Basel)最新文献

{"title":"Approaches for Identifying LncRNA-Associated Proteins for Therapeutic Targets and Cancer Biomarker Discovery.","authors":"Mohammad Shabir Hussain, Puneet Vij, Sudhir Kotnala, Shadab Ahmad, Subhash C Chauhan, Manish K Tripathi","doi":"10.3390/targets3030027","DOIUrl":"https://doi.org/10.3390/targets3030027","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and cellular signaling in cancer. Their functions are primarily mediated through interactions with specific protein partners that modulate chromatin structure, epigenetic remodeling, transcription, and signal transduction. In this review, we explore reports and strategies for the proteomic characterization of lncRNA-associated proteins, particularly emphasizing high-throughput liquid chromatography-mass spectrometry (LC-MS)-based techniques. Affinity-based methods such as RNA pull-down, ChIRP MS, RAP-MS, BioID-MS, and SILAC-MS enable sensitive and specific mapping of lncRNA and protein complexes. These approaches reveal cancer-specific proteomic signatures, post-translational modifications, and mechanistic insights into tumor biology. The use of label-free quantification, bituminization, and crosslinking strategies further enhances the resolution of dynamic RNA-protein networks. Validation tools following bioinformatic analyses, such as Western blotting, immunohistochemistry, immunofluorescence, and ELISA, are used to prioritize and confirm findings. Candidate biomarkers from hepatocellular carcinoma to colorectal and prostate cancers, profiling lncRNA-associated proteins, hold promise for identifying clinically actionable biomarkers and therapeutic targets. This review highlights the translational relevance of lncRNA protein studies and advocates for their broader adoption in oncological research. In LC-MS workflows, proteins bound to lncRNAs are enzymatically digested into peptides, separated via nano-LC, and analyzed using high-resolution tandem MS. Label-free or isotope-labeled methods quantify differential enrichment, followed by bioinformatics-driven pathway annotation.</p>","PeriodicalId":520405,"journal":{"name":"Targets (Basel)","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathology and Therapeutic Significance of Fibroblast Growth Factors.","authors":"Oshadi Edirisinghe, Gaëtane Ternier, Thallapuranam Krishnaswamy Suresh Kumar","doi":"10.3390/targets3010005","DOIUrl":"https://doi.org/10.3390/targets3010005","url":null,"abstract":"<p><p>The fibroblast growth factor (FGF) family includes 22 proteins in humans. Based on their mode of action, there are three families of FGFs: paracrine FGFs (FGF 1-10, 16, 17, 18, 20, and 22), intracrine FGFs (FGF 11-14), and endocrine FGFs (FGF 19, 21, and 23). FGF signaling plays critical roles in embryonic development, tissue repair, regeneration, angiogenesis, and metabolic regulation. They exert their cellular functions by binding, dimerization, and activation of transmembrane FGF receptors (FGFRs). Aberrant FGF signaling is associated with various human diseases. Thus, understanding the unique properties of FGF signaling will help to explore new therapeutic interventions against FGF-mediated pathological conditions. This review will discuss the differential expression and regulation of each FGF under normal human physiological and pathological conditions. Moreover, we will outline current therapeutics and treatment strategies that have been developed against FGF-related pathology.</p>","PeriodicalId":520405,"journal":{"name":"Targets (Basel)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147314255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bombesin Receptor Subtype-3 Regulates Tumor Growth by HER2 Tyrosine Phosphorylation in a Reactive Oxygen Species-Dependent Manner in Lung Cancer Cells.","authors":"Terry W Moody, Irene Ramos-Alvarez, Samuel A Mantey, Robert T Jensen","doi":"10.3390/targets3010007","DOIUrl":"https://doi.org/10.3390/targets3010007","url":null,"abstract":"<p><p>Bombesin receptor subtype-3 (BRS-3) is a type 1 G-protein-coupled receptor. BRS-3 is an orphan GPCR which is structurally related to the neuromedin B and gastrin-releasing peptide receptors. When activated, BRS-3 causes phosphatidylinositol turnover in lung cancer cells. BRS-3 stimulates tyrosine phosphorylation of the epidermal growth-factor receptor (ErbB1), however it is unknown if it transactivates ErbB2/HER2. Adding the nonpeptide BRS-3 allosteric-agonist, MK-5046 or the peptide agonist, BA1 to the lung cancer cell line, NCI-H727 or BRS-3-transfected NCI-H1299 lung cancer cells, increased tyrosine phosphorylation of HER2/ERK2. This increase was antagonized by the BRS-3 peptide antagonist, Bantag-1 and the small molecule BRS-3 antagonist, ML-18. The increase in HER2/ERK phosphorylation caused by MK-5046 was inhibited by ROS inhibitors, N-acetylcysteine and Tiron (superoxide-scavenger). Adding MK-5046 to lung cancer cells increased reactive-oxygen species which was inhibited by NAC or Tiron. MK-5024 and BA1 increased NSCLC colony formation whereas, Bantag-1/ML-18 inhibited proliferation. These results indicate that in lung cancer cells activation of BRS-3 regulates HER2-transactivation in ROS-dependent manner which can mediate tumor growth. These results raise the possibility that the use of HER2-inhibiting compounds alone or in combination with other agents, could be a novel approach in the treatment of these tumors.</p>","PeriodicalId":520405,"journal":{"name":"Targets (Basel)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing FDA-Approved Drugs Against Potential Drug Targets Involved in Brain Inflammation Contributing to Alzheimer's Disease.","authors":"Catherine Sharo, Jiayu Zhang, Tianhua Zhai, Jingxuan Bao, Andrés Garcia-Epelboim, Elizabeth Mamourian, Li Shen, Zuyi Huang","doi":"10.3390/targets2040025","DOIUrl":"10.3390/targets2040025","url":null,"abstract":"<p><p>Alzheimer's disease is a neurodegenerative disease that continues to have a rising number of cases. While extensive research has been conducted in the last few decades, only a few drugs have been approved by the FDA for treatment, and even fewer aim to be curative rather than manage symptoms. There remains an urgent need for understanding disease pathogenesis, as well as identifying new targets for further drug discovery. Alzheimer's disease (AD) is known to stem from a build-up of amyloid beta (Aβ) plaques as well as tangles of tau proteins. Furthermore, inflammation in the brain is known to arise from the degeneration of tissue and the build-up of insoluble material. Therefore, there is a potential link between the pathology of AD and inflammation in the brain, especially as the disease progresses to later stages where neuronal death and degeneration levels are higher. Proteins that are relevant to both brain inflammation and AD thus make ideal potential targets for therapeutics; however, the proteins need to be evaluated to determine which targets would be ideal for potential drug therapeutic treatments, or 'druggable'. Druggability analysis was conducted using two structure-based methods (i.e., Drug-Like Density analysis and SiteMap), as well as a sequence-based approach, SPIDER. The most druggable targets were then evaluated using single-nuclei sequencing data for their clinical relevance to inflammation in AD. For each of the top five targets, small molecule docking was used to evaluate which FDA approved drugs were able to bind with the chosen proteins. The top targets included DRD2 (inhibits adenylyl cyclase activity), C9 (binds with C5B8 to form the membrane attack complex), C4b (binds with C2a to form C3 convertase), C5AR1 (GPCR that binds C5a), and GABA-A-R (GPCR involved in inhibiting neurotransmission). Each target had multiple potential inhibitors from the FDA-approved drug list with decent binding infinities. Among these inhibitors, two drugs were found as top inhibitors for more than one protein target. They are C15H14N2O2 and v316 (Paracetamol), used to treat pain/inflammation originally for cataracts and relieve headaches/fever, respectively. These results provide the groundwork for further experimental investigation or clinical trials.</p>","PeriodicalId":520405,"journal":{"name":"Targets (Basel)","volume":"2 4","pages":"446-469"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}