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1.
Pathol Res Pract ; 260: 155446, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39004001

RESUMO

Osteoarthritis (OA) poses a significant global health challenge, with its prevalence anticipated to increase in the coming years. This review delves into the emerging molecular biomarkers in OA pathology, focusing on the roles of various molecules such as metabolites, noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Advances in omics technologies have transformed biomarker identification, enabling comprehensive analyses of the complex pathways involved in OA pathogenesis. Notably, ncRNAs, especially miRNAs and lncRNAs, exhibit dysregulated expression patterns in OA, presenting promising opportunities for diagnosis and therapy. Additionally, the intricate interplay between epigenetic modifications and OA progression highlights the regulatory role of epigenetics in gene expression dynamics. Genome-wide association studies have pinpointed key genes undergoing epigenetic changes, providing insights into the inflammatory processes and chondrocyte hypertrophy typical of OA. Understanding the molecular landscape of OA, including biomarkers and epigenetic mechanisms, holds significant potential for developing innovative diagnostic tools and therapeutic strategies for OA management.

2.
Biomed Pharmacother ; 177: 116954, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38906027

RESUMO

Osteoporosis, characterized by compromised bone density and microarchitecture, represents a significant global health challenge, particularly in aging populations. This comprehensive review delves into the intricate signaling pathways implicated in the pathogenesis of osteoporosis, providing valuable insights into the pivotal role of signal transduction in maintaining bone homeostasis. The exploration encompasses cellular signaling pathways such as Wnt, Notch, JAK/STAT, NF-κB, and TGF-ß, all of which play crucial roles in bone remodeling. The dysregulation of these pathways is a contributing factor to osteoporosis, necessitating a profound understanding of their complexities to unveil the molecular mechanisms underlying bone loss. The review highlights the pathological significance of disrupted signaling in osteoporosis, emphasizing how these deviations impact the functionality of osteoblasts and osteoclasts, ultimately resulting in heightened bone resorption and compromised bone formation. A nuanced analysis of the intricate crosstalk between these pathways is provided to underscore their relevance in the pathophysiology of osteoporosis. Furthermore, the study addresses some of the most crucial long non-coding RNAs (lncRNAs) associated with osteoporosis, adding an additional layer of academic depth to the exploration of immune system involvement in various types of osteoporosis. Finally, we propose that SKP1 can serve as a potential biomarker in osteoporosis.

3.
Int J Biol Macromol ; 270(Pt 1): 132239, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38735606

RESUMO

Colorectal cancer (CRC) is a major worldwide health issue, with high rates of both occurrence and mortality. Dysregulation of the transforming growth factor-beta (TGF-ß) signaling pathway is recognized as a pivotal factor in CRC pathogenesis. Notably, the INHBA gene and long non-coding RNAs (lncRNAs) have emerged as key contributors to CRC progression. The aim of this research is to explore the immunological roles of INHBA and PELATON in CRC through a combination of computational predictions and experimental validations, with the goal of enhancing diagnostic and therapeutic strategies. In this study, we utilized bioinformatics analyses, which involved examining differential gene expression (DEG) in the TCGA-COAD dataset and exploring the INHBA gene in relation to the TGF-ß pathway. Additionally, we analyzed mutations of INHBA, evaluated the microenvironment and tumor purity, investigated the INHBA's connection to immune checkpoint inhibitors, and measured its potential as an immunotherapy target using the TIDE score. Utilizing bioinformatics analyses of the TCGA-COAD dataset beside experimental methodologies such as RT-qPCR, our investigation revealed significant upregulation of INHBA in CRC. As results, our analysis of the protein-protein interaction network associated with INHBA showed 10 interacting proteins that play a role in CRC-associated processes. We observed a notable prevalence of mutations within INHBA and explored its correlation with the response to immune checkpoint inhibitors. Our study highlights INHBA as a promising target for immunotherapy in CRC. Moreover, our study identified PELATON as a closely correlated lncRNA with INHBA, with experimental validation confirming their concurrent upregulation in CRC tissues. Thus, these findings highlight the importance of INHBA and PELATON in driving CRC progression, suggesting their potential utility as diagnostic and prognostic biomarkers. By integrating computational predictions with experimental validations, this research enhances our understanding of CRC pathogenesis and uncovers prospects for personalized therapeutic interventions.


Assuntos
Neoplasias Colorretais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Subunidades beta de Inibinas , Mapas de Interação de Proteínas , Transdução de Sinais , Fator de Crescimento Transformador beta , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Humanos , Biologia Computacional/métodos , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética , Mapas de Interação de Proteínas/genética , Subunidades beta de Inibinas/genética , Subunidades beta de Inibinas/metabolismo , RNA Longo não Codificante/genética , Microambiente Tumoral/genética , Mutação , Biomarcadores Tumorais/genética
4.
Pathol Res Pract ; 253: 155014, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128189

RESUMO

This review examines and compares the diagnostic and prognostic capabilities of miRNAs and lncRNAs derived from pseudogenes in cancer patients. Additionally, it delves into their roles in cancer pathogenesis. Both miRNAs and pseudogene-derived lncRNAs have undergone thorough investigation as remarkably sensitive and specific cancer biomarkers, offering significant potential for cancer detection and monitoring. . Extensive research is essential to gain a complete understanding of the precise roles these non-coding RNAs play in cancer, allowing the development of novel targeted therapies and biomarkers for improved cancer detection and treatment approaches.


Assuntos
MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , Pseudogenes/genética , Neoplasias/diagnóstico , Neoplasias/genética , Prognóstico , Biomarcadores Tumorais/genética
5.
Pathol Res Pract ; 253: 155036, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38134836

RESUMO

Osteoporosis, a prevalent bone disorder influenced by genetic and environmental elements, significantly increases the likelihood of fractures and bone weakness, greatly affecting the lives of those afflicted. Yet, the exact epigenetic processes behind the onset of osteoporosis are still unclear. Growing research indicates that epigenetic changes could act as vital mediators that connect genetic tendencies and environmental influences, thereby increasing the risk of osteoporosis and bone fractures. Within these epigenetic factors, certain types of RNA, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been recognized as key regulatory elements. These RNA types wield significant influence on gene expression through epigenetic regulation, directing various biological functions essential to bone metabolism. This extensive review compiles current research uncovering the complex ways in which miRNAs, lncRNAs, and circRNAs are involved in the development of osteoporosis, especially in osteoblasts and osteoclasts. Gaining a more profound understanding of the roles these three RNA classes play in osteoporosis could reveal new diagnostic methods and treatment approaches for this incapacitating condition. In conclusion, this review delves into the complex domain of epigenetic regulation via non-coding RNA in osteoporosis. It sheds light on the complex interactions and mechanisms involving miRNAs, lncRNAs, and circRNAs within osteoblasts and osteoclasts, offering an in-depth understanding of the less explored aspects of osteoporosis pathogenesis. These insights not only reveal the complexity of the disease but also offer significant potential for developing new diagnostic methods and targeted treatments. Therefore, this review marks a crucial step in deciphering the elusive complexities of osteoporosis, leading towards improved patient care and enhanced quality of life.


Assuntos
MicroRNAs , Osteoporose , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Circular/genética , Epigênese Genética/genética , Qualidade de Vida , MicroRNAs/genética , Osteoporose/genética
6.
Prog Biophys Mol Biol ; 180-181: 49-82, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37059270

RESUMO

Over the last four decades, methodological innovations have continuously changed transcriptome profiling. It is now feasible to sequence and quantify the transcriptional outputs of individual cells or thousands of samples using RNA sequencing (RNA-seq). These transcriptomes serve as a connection between cellular behaviors and their underlying molecular mechanisms, such as mutations. This relationship, in the context of cancer, provides a chance to unravel tumor complexity and heterogeneity and uncover novel biomarkers or treatment options. Since colon cancer is one of the most frequent malignancies, its prognosis and diagnosis seem to be critical. The transcriptome technology is developing for an earlier and more accurate diagnosis of cancer which can provide better protectivity and prognostic utility to medical teams and patients. A transcriptome is a whole set of expressed coding and non-coding RNAs in an individual or cell population. The cancer transcriptome includes RNA-based changes. The combined genome and transcriptome of a patient may provide a comprehensive picture of their cancer, and this information is beginning to affect treatment decision-making in real-time. A full assessment of the transcriptome of colon (colorectal) cancer has been assessed in this review paper based on risk factors such as age, obesity, gender, alcohol use, race, and also different stages of cancer, as well as non-coding RNAs like circRNAs, miRNAs, lncRNAs, and siRNAs. Similarly, they have been examined independently in the transcriptome study of colon cancer.


Assuntos
Neoplasias do Colo , MicroRNAs , Humanos , Transcriptoma/genética , MicroRNAs/genética , Perfilação da Expressão Gênica , Neoplasias do Colo/genética , Biomarcadores , Redes Reguladoras de Genes
7.
Biomed Pharmacother ; 153: 113338, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35779418

RESUMO

Obesity is one of the risk factors concerns of colorectal cancer (CRC), the most common type of gastrointestinal cancer, due to the changing lifestyle and especially diet. There are various molecular pathways associated with obesity and the risk of CRC incidence, such as insulin resistance or elevated plasma free fatty acids, which alter the signaling pathways of intestinal epithelial cells. The aim of this study was to better understand the significance of unsaturated fatty acid biosynthesis on pathogenesis of colon cancer in obese. Based on GSE20931 dataset, obese individuals affected by CRC had higher increased gene expression than non-obese individuals. The analysis showed that in obese individuals, the 16 signaling pathway genes were activated and increased (FDR <0.05) significantly. The biosynthetic pathway of unsaturated fatty acids showed a cross-talk with the arachidonic acid metabolism pathway and the PPAR signaling pathway is influenced and regulated via these pathways. The biosynthetic pathway of unsaturated fatty acids consisting of 22 genes, were analyzed using GEO data and revealed that 4 genes (HSD17B12, TECR, FADS2, ELOVL5) from this pathway were significantly increased (FDR <0.05). These data were validated based on TCGA data (Adj.p.value <0.001). The expression level of candidate genes in HT-29 cells decreased significantly (P.value <0.01), and PPARγ expression increased under linoleic acid treatment (200 µM) compared to control cells. Moreover, in presence of linoleic acid treatment, migration, colony formation, and proliferation decreased (P.value <0.01) in presence of treatment. In summary, the Biosynthesis pathway of unsaturated fatty acids is an interesting and critical pathway in CRC.


Assuntos
Neoplasias Colorretais , Ácidos Graxos Insaturados , Obesidade , Adipogenia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ácidos Graxos Insaturados/biossíntese , Humanos , Resistência à Insulina , Ácido Linoleico , Obesidade/metabolismo
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