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This article explores the field of cancer genetics and epigenetics, emphasizing the importance of understanding the genetic and epigenetic mechanisms of cancer for effective treatment. It discusses various research topics within this field, such as the role of MTAP deficiency, manipulation of ERBB2 mRNA sequences, and the use of ferroptosis as a biomarker and treatment for ovarian cancers. The article also mentions the association of MTHFR gene polymorphisms with prostate cancer risk, noting that this influence is specific to certain populations. Overall, the article highlights the need for further research to identify biomarkers, mechanisms of cancer development, and drug resistance, and emphasizes the potential of precision diagnostics and treatments in cancer care. [Extracted from the article]

Microphthalmia-associated transcription factor (MITF) is a master regulatory factor for melanocytes. MITF regulates multiple pigmentary genes for maintaining cellular homeostasis. MicroRNAs (miRNAs) play crucial roles in numerous biological processes however their molecular/cellular mechanisms to regulate pigmentation have not been fully explored. This study was undertaken to investigate the role of miRNAs in skin depigmentation via regulation of MITF gene. Depigmentation in C57BL/6 black mice was induced by an autoimmune response against tyrosinase. Bioinformatics approach was used to detect miRNAs conserved in 3′untraslated region (3′UTR) of MITF mRNA. The iMC23 mouse melanocytes were used for transfection experiments. The data demonstrated that the MITF mRNA/protein was markedly low in lesional skin of depigmented mice (p < 0.05). Targetscan genomic database determined that 3′UTR of mouse MITF constitutes 4819 nucleotide bases and has 23 conserved sites for different miRNAs To validate the pairing of these predicted miRNAs with MITF mRNA, five miRNAs were deregulated in lesional skin (p < 0.05). Among them, mmu-miR-181a-5p and mmu-miR-183-5p were up-regulated, whereas mmu-miR-26a-5p, mmu-miR-26b-5p and mmu-miR-32-5p were down-regulated (p < 0.05). To verify these results, the iMC23 mouse melanocytes were used. Transfection of iMC23 cells with specific miRNAs mimics or inhibitors or with 3'UTR reporter clone of MITF, showed only mmu-miR-183-5p binds to 3'UTR of MITF mRNA and regulates its expression in iMC23 melanocytes. In conclusions, this is the first study shows that miR-183-5p is a direct regulator of MITF in iMC23 melanocytes. Thus, miR-183-5p is an important regulator of melanocytes homeostasis and may be a novel target for autoimmune depigmentation therapy. [ABSTRACT FROM AUTHOR]

Objectives: Honey total polyphenolic fraction (HTPF) is reported to have anti-disease potential, however the role of HTPF in the regulation of microRNAs (miRNAs) has never been investigated. This study was undertaken to investigate the potential of HTPF against inflammation via regulation of miRNAs in pancreatic islets of Langerhans. Methods: Pancreatic islets were isolated from C57BL/6 mice and HTPF was purified from honey. Bioinformatics algorithms were used to determine miRNA target genes. Expression of miRNA and mRNA was determined using their specific taqman assays. Pairing between miRNA and 30 untranslated region (30UTR) of mRNA was confirmed using luciferase reporter clone containing the 30UTR of mRNA sequences and results were verified by transfection of mouse pancreatic β-cell line Min6 with miRNA inhibitors. Results: The data showed that mmu-miR-26a-5p is a direct regulator of cyclooxygenase-2 (COX-2) expression and HTPF inhibits COX-2 expression or prostaglandin E2 (PGE2) production via up-regulating mmu-miR-26a-5p expression. Transfection of islets with anti-miR-26a-5p significantly enhanced COX-2 expression and PGE2 production (p < .01), while HTPF treatment significantly inhibited anti-miR-26a-5p transfection-induced COX-2 expression or PGE2 production (p < .05). These findings were further verified in pancreatic β-cells Min6. Moreover, the data also determined that HTPF also inhibits glucose-induced nuclear transcription factor (NF)-κB activity. Conclusion: HTPF suppresses glucose-induced PGE2 production and activation of NF-κB via negative regulation of COX-2 and mmu-miR26a-5p. These novel pharmacological actions of HTPF on glucose-stimulated pancreatic islets provide new suggestions that HTPF or HTPF-derived compounds inhibit glucose induced inflammation in pancreas by up-regulating the expression of microRNAs. [ABSTRACT FROM AUTHOR]

Purpose: MicroRNAs (miRNAs) are short, non-coding RNAs involved in almost all cellular processes. Epigallocatechin-3-O-gallate (EGCG) is a green tea polyphenol and is known to exert anti-arthritic effects by inhibiting genes associated with osteoarthritis (OA). This study was undertaken to investigate the global effect of EGCG on interleukin-1β (IL-1β)-induced expression of miRNAs in human chondrocytes.Methods: Human chondrocytes were derived from OA cartilage and then treated with EGCG and IL-1β. Human miRNA microarray technology was used to determine the expression profile of 1347 miRNAs. Microarray results were verified by taqman assays and transfection of chondrocytes with miRNA inhibitors.Results: Out of 1347 miRNAs, EGCG up-regulated expression of 19 miRNAs and down-regulated expression of 17 miRNAs, whereas expression of 1311 miRNAs remains unchanged in IL-1β-stimulated human OA chondrocytes. Bioinformatics approach showed that 3`UTR of ADAMTS5 mRNA contains the ‘seed-matched-sequence’ for hsa-miR-140-3p. IL-1β-induced expression of ADAMTS5 correlated with down-regulation of hsa-miR-140-3p. Importantly, EGCG inhibited IL-1β-induced ADAMTS5 expression and up-regulated the expression of hsa-miR-140-3p. This EGCG-induced co-regulation between ADAMTS5 and hsa-miR-140-3p becomes reversed in OA chondrocytes transfected with anti-miR-140-3p.Conclusions: This study provides an important insight into the molecular basis of the reported anti-arthritic effects of EGCG. Our data indicate that the potential of EGCG in OA chondrocytes may be related to its ability to globally inhibit inflammatory response via modulation of miRNAs expressions. [ABSTRACT FROM AUTHOR]

Inflammatory-mediated reactions have been implicated as contributors in a number of dermatological disorders, including psoriasis. However, the potential of interleukin (IL)-32 and its isoforms to contribute to the pathogenesis of psoriasis remains unexplored. This study was undertaken to investigate the role of IL-32 and its isoforms IL-32 α, IL-32β, IL-32γ, and IL-32δ in the peripheral blood of psoriatic patients. The majority of chronic plaque psoriatic patients showed elevated IL-32 mRNA levels in the peripheral blood mononuclear cells (PBMCs) as compared with the levels of IL-32 mRNA in PBMCs of healthy controls (p = 0.001). To further investigate the role of elevated levels of IL-32 in psoriatic patients, IL-32 isoforms mRNAs were determined. All tested isoforms IL-32α, IL-32β, IL-32γ, and IL-32δ were overexpressed in psoriatic patients PBMCs as compared with healthy controls' PBMCs (p < 0.05). IL-32α mRNA expression was also significantly higher as compared with all other isoforms of IL-32 in PBMCs of psoriatic patients (p < 0.001). In short, this is the first study that shows the role of IL-32 and its isoforms in the peripheral blood of psoriatic patients. Our novel findings support an association between elevated levels of IL-32 and psoriasis. The data also suggest that a major proinflammatory response of IL-32 may derive from IL-32α isoform in psoriasis. [ABSTRACT FROM AUTHOR]

Osteoarthritis ( OA) is a most common form of arthritis worldwide leading to significant disability. Micro RNAs (mi RNAs) are non-coding RNAs involved in various aspects of cartilage development, homoeostasis and pathology. Several mi RNAs have been identified which have shown to regulate expression of target genes relevant to OA pathogenesis such as matrix metalloproteinase ( MMP)-13, cyclooxygenase ( COX)-2, etc. Epigallocatechin-3- O-gallate ( EGCG), the most abundant and active polyphenol in green tea, has been reported to have anti-arthritic effects, however, the role of EGCG in the regulation of mi RNAs has not been investigated in OA. Here, we showed that EGCG inhibits COX-2 mRNA/protein expression or prostaglandin E2 ( PGE2) production via up-regulating micro RNA hsa-miR-199a-3p expression in interleukin ( IL)-1β-stimulated human OA chondrocytes. This negative co-regulation of hsa-miR-199a-3p and COX-2 by EGCG was confirmed by transfection of OA chondrocytes with anti-miR-199a-3p. Transfection of OA chondrocytes with anti-miR-199a-3p significantly enhanced COX-2 expression and PGE2 production ( P < 0.001), while EGCG treatment significantly inhibited anti-miR-199a-3p transfection-induced COX-2 expression or PGE2 production in a dose-dependent manner. These results were further re-validated by co-treatment of these transfection OA chondrocytes with IL-1β and EGCG. EGCG treatment consistently up-regulated the IL-1β-decreased hsa-miR-199a-3p expression ( P < 0.05) and significantly inhibited the IL-1β-induced COX-2 expression/ PGE2 production ( P < 0.05) in OA chondrocytes transfected with anti-hsa-miR-199a-3p. Taken together, these results clearly indicate that EGCG inhibits COX-2 expression/ PGE2 production via up-regulation of hsa-miR-199a-3p expression. These novel pharmacological actions of EGCG on IL-1β-stimulated human OA chondrocytes provide new suggestions that EGCG or EGCG-derived compounds inhibit cartilage breakdown or pain by up-regulating the expression of micro RNAs in human chondrocytes. [ABSTRACT FROM AUTHOR]

This study was undertaken to identify and characterize the globally expressed microRNAs (miRNAs) involved in interleukin-1β (IL-1β)-induced joint damage and to predict whether miRNAs can regulate the catabolic effects in osteoarthritis (OA) chondrocytes. Out of 1347 miRNAs analyzed by microarrays in IL-1β-stimulated OA chondrocytes, 35 miRNAs were down-regulated, 1 miRNA was up-regulated, and the expression of 1311 miRNAs remained unchanged. Bioinformatics analysis showed the key inflammatory mediators and key molecular pathways are targeted by differentially expressed miRNAs. Novel miRNAs identified could have important diagnostic and therapeutic potentials in the development of novel therapeutic strategies for pain managements in OA. [ABSTRACT FROM PUBLISHER]

Inducible nitric oxide synthase (iNOS) expression is associated with the pathogenesis of osteoarthritis (OA). This study was undertaken to investigate whether interleukin-1β (IL-1β)-mediated induction of iNOS can be regulated by microRNA-26a-5p (hsa-miR-26a-5p) in OA. Bioinformatics approaches show that 3′UTR of iNOS mRNA contained the ‘seed-matched-sequence’ for hsa-miR-26a-5p. IL-1β-induced expression of iNOS correlated with the down-regulation of miR-26a-5p in human OA chondrocytes. hsa-miR-26a-5p directly suppressed the luciferase activity of 3′UTR-iNOS reporter clone. Transfection with pre-miR-26a-5p induced marked silencing of iNOS expression. Activation of NF-κB pathway down-regulated the expression of hsa-miR-26a-5p and induced iNOS expression. In short, this is the first report that shows hsa-miR-26a-5p is a direct regulator of iNOS expression in human chondrocytes. hsa-miR-26a-5p may be an important regulator of human cartilage homeostasis and a new target for OA therapy. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: During aging, advanced glycation end products (AGEs) accumulate in articular cartilage. In this study we determined whether AGEs induce endoplasmic reticulum (ER) stress and studied the ER stress-activated pathways that stimulate cyclooxygenase-2 (COX-2) expression in human chondrocytes. Methods: Chondrocytes were stimulated with AGE-BSA. Gene expression was determined by quantitative PCR and protein expression was studied by immunoblotting. Studies to elucidate involved pathways were executed using siRNAs and specific inhibitors of eukaryotic initiation factor-2α (eIF2α), MAPKs and NF-κB. Results: AGE-BSA induced expression of GRP78 with concomitant increase in COX-2 expression was observed in human chondrocytes. In addition, expression of Bag-1, an ER stress marker was also increased by AGE-BSA. RAGE knockdown inhibited AGE-BSA-induced expression of GRP78 and COX-2. Treatment with eIF2α inhibitor or eIF2α knockdown inhibited AGE-BSA-induced expression of GRP78 and COX-2 with decreased PGE2 production. Treatment with SB202190 inhibited AGE-BSA-induced expression of GRP78 and COX-2, while treatment with PD98051 inhibited AGE-BSA-induced GRP78 protein expression but had no effect on COX-2 protein expression. SP600125 had no effect on either GRP78 or COX-2 protein expression. Bay 11-7082 suppressed AGE-BSA-induced GRP78 and COX-2 expression. AGE-BSA-induced activation of NF-κB was inhibited by treatment with SB202190 and by eIF2α knockdown, but was not inhibited when chondrocytes were treated with SP600125 or PD98059. Conclusion: This study demonstrates that AGEs induce ER stress and stimulate the expression of COX-2 through eIF2α, p38-MAPK and NF-κB pathways in human chondrocytes. Our results provide important insights into cartilage degradation in osteoarthritis associated with latent ER stress. [Copyright &y& Elsevier]

The article presents a study regarding the regulation of microRNA on the matrix metalloproteinases (MMPs) expression in human osteoarthritis (OA) chondrocytes. It states that interleukin-1β (IL-1β) in vitro was used to stimulate chondrocytes while TaqMan for quantifying gene expression. The results show that 2 microRNA were up-regulated while 42 microRNA were down-regulated in IL-β—stimulated OA chondrocytes.