DNA and cell biology最新文献

Breast cancer (BC) is a significant contributor to cancer-related deaths in women, and it has complex connections with obesity and aging. This review explores the interaction between obesity and aging in relation to the development and progression of BC, focusing on the controlling role of microRNAs (miRNAs). Obesity, characterized by excess adipose tissue, contributes to a proinflammatory environment and metabolic dysregulation, which are important in tumor development. Aging, associated with cellular senescence and systemic changes, further exacerbates these conditions. miRNAs, small noncoding RNAs that regulate gene expression, play key roles in these processes, impacting pathways involved in cell proliferation, apoptosis, and cancer metastasis, either as tumor suppressors or oncogenes. Importantly, specific miRNAs are implicated in mediating the impact of obesity and aging on BC. Exploring the regulatory networks controlled by miRNAs provides valuable information on new targets for therapy and predictive markers, demonstrating the potential for using miRNA-based interventions to treat BC in obese and elderly individuals. This review emphasizes the importance of integrated research strategies to understand the complex connections between obesity, aging, and miRNA regulation in BC.

According to the World Health Organization, Mycobacterium tuberculosis infections affect approximately 25% of the world's population. There is mounting evidence linking autophagy and immunological dysregulation to tuberculosis (TB). As a result, this research set out to discover TB-related autophagy-related biomarkers and prospective treatment targets. We used five autophagy databases to get genes linked to autophagy and Gene Expression Omnibus databases to get genes connected to TB. Then, functional modules associated with autophagy were obtained by analyzing them using weighted gene co-expression network analysis. Both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to examine the autophagy-related genes (ATGs) of important modules. Limma was used to identify differentially expressed ATGs (DE-ATGs), and the external datasets were used to further confirm their identification. We used DE-ATGs and a protein-protein interaction network to search the hub genes. CIBERSORT was used to estimate the kinds and amounts of immune cells. After that, we built a drug-gene interaction network and a network that included messenger RNA, small RNA, and DNA. At last, the differential expression of hub ATGs was confirmed by RT-qPCR, immunohistochemistry, and western blotting. The diagnostic usefulness of hub ATGs was evaluated using receiver operating characteristic curve analysis. Including 508 ATGs, four of the nine modules strongly linked with TB were deemed essential. Interleukin 1B (IL1B), CAPS1, and signal transducer and activator of transcription 1 (STAT1) were identified by intersection out of 22 DE-ATGs discovered by differential expression analysis. Research into immune cell infiltration found that patients with TB had an increased proportion of plasma cells, CD8 T cells, and M0 macrophages. A competitive endogenous RNA network utilized 10 long non-coding RNAs and 2 miRNAs. Then, the IL1B-targeted drug Cankinumad was assessed using this network. During bioinformatics analysis, three hub genes were validated in mouse and macrophage infection models. We found that IL1B, CASP1, and STAT1 are important biomarkers for TB. As a result, these crucial hub genes may hold promise as TB treatment targets.

The number of cases of papillary thyroid cancer (PTC) has gone up significantly in recent years, with high recurrence. Numerous reports have highlighted the participation of circular RNAs (circRNAs) in regulating the advancement of cancers, including PTC. Furthermore, recent studies suggest that N6-methyladenosine (m6A) modified circRNAs play pivotal roles in cancer progression. Hence, we studied the potential role of a novel circRNA, hsa_circ_0136959, and its regulatory mechanism on m6A modification by methyltransferase-like 3 (METTL3) in the tumor characteristics of PTC. The expressions of hsa_circ_0136959 and METTL3 were evaluated in PTC samples and cell lines via quantitative real-time polymerase chain reaction. The effect of hsa_circ_0136959 on the malignant properties of PTC was analyzed by performing Cell Counting Kit-8, colony formation, and transwell assays. In addition, its effects on the levels of markers related to ferroptosis (reactive oxygen species, Fe²⁺, and iron) in PTC cells were also assessed. Bioinformatics analysis was done to determine the hsa_circ_0136959 expression and m6A modification sites on it in PTC. The m6A level of hsa_circ_0136959 was analyzed through methylated (m6A) RNA immunoprecipitation. The hsa_circ_0136959 was observed to be downregulated in both PTC samples and cells. In vitro experiments showed that its overexpression impeded the malignant properties of PTC cells. Moreover, hsa_circ_0136959 overexpression increased the levels of ferroptosis-related markers in PTC cells. We also found that METTL3 was notably reduced in PTC samples and was positively correlated with hsa_circ_0136959. Mechanistically, METTL3 enhanced hsa_circ_0136959 expression through m6A modification. Our results demonstrate that METTL3-mediated m6A modification elevated hsa_circ_0136959 expression and subsequently restricted the tumor characteristics of PTC by accelerating ferroptosis.

Liver fibrosis (LF) is a clinical disorder characterized by inflammation and excessive accumulation of extracellular matrix (ECM). This study investigates the effects of the antifibrotic compound pirfenidone (PFD) on improving LF through histological changes and modulation of eukaryotic translation initiation factor 6 (eIF6), P311, and transforming growth factor beta (TGF-β) in rats with bile duct ligation (BDL)-induced LF. Rats received daily doses of PFD (200 and 500 mg/kg) for 4 weeks. The study encompassed biochemical, pathological, and immunohistochemical (IHC) analyses. mRNA levels of eIF6, P311, TGF-β, ECM deposition, hepatic stellate cell (HSC) activation, and inflammatory mediator genes were measured by RT-qPCR. Protein levels of eIF6, P311, and TGF-β were detected by western blotting. Compared with the BDL group, PFD dose-dependently reduced hydroxyproline content, liver index, biochemical parameters, fibrosis score, and fibrosis area. PFD also modulated BDL-induced hepatic inflammation, ECM accumulation, and HSC activation. IHC staining of Ki-67 and hepatocyte paraffin-1 revealed that PFD enhanced liver regeneration. The research confirmed that PFD gradually downregulated elevated eIF6, P311, and TGF-β levels in BDL-induced LF. These findings suggest that PFD could be a potential treatment for LF, as it may help attenuate fibrosis and enhance liver regeneration, possibly through the modulation of these specific markers.

Lung cancer represents a significant global health burden, with non-small cell lung cancer (NSCLC) being the most common subtype. The current standard of care for NSCLC has limited efficacy, highlighting the necessity for innovative treatment options. Lidocaine, traditionally recognized as a local anesthetic, has emerged as a compound with potential antitumor and anti-inflammatory capabilities. This study was designed to explore the impact of lidocaine on NSCLC cell proliferation and inflammation, particularly focusing on the Toll-like receptor 9 (TLR)-9/MyD88/NF-κB signaling pathway. A nude mice model of NSCLC was employed, with animals receiving lidocaine at different concentrations. In vitro experiments on A549 cells involved exposure to lidocaine, followed by assessment of cell viability, cytokine expression, and TLR-9 levels using the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, enzyme-linked immunosorbent assay, and Quantitative Real-time polymerase chain reaction (qPCR). Protein levels were evaluated via Western blot analysis. Additionally, A549 cells were transfected with a TLR-9-overexpressing lentivirus to dissect the role of TLR-9 in lidocaine's mechanism of action. Treatment with lidocaine led to a significant reduction in tumor dimensions and a decrease in inflammatory marker expression in the NSCLC mouse model. In cellular assays, lidocaine effectively suppressed A549 cell proliferation and the expression of inflammatory cytokines. The overexpression of TLR-9 partially negated the suppressive effects of lidocaine, underscoring the significance of the TLR-9/MyD88/NF-κB pathway in mediating lidocaine's effects. Lidocaine's inhibitory effects on NSCLC cell proliferation and its anti-inflammatory mechanisms are mediated through the TLR-9/MyD88/NF-κB pathway. The study's results offer promising insights into the therapeutic potential of lidocaine in NSCLC and pave the way for future investigations into its application in cancer therapy.

Long noncoding RNAs (lncRNAs) have emerged as critical regulators in the development of colorectal cancer (CRC). Previous studies indicate that lncRNA FEZF1-AS1 is highly expressed in CRC, but its role in modulating CRC via the P53 signaling pathway remains unclear. In this study, we found that FEZF1-AS1 promotes the growth of the CRC cell line (HCT116) and drives epithelial-mesenchymal transition (EMT) through the P53 signaling pathway. Our data showed that FEZF1-AS1 expression is significantly upregulated in HCT116, and elevated levels of FEZF1-AS1 are associated with poor prognosis in patients with CRC. In addition, the knockdown of FEZF1-AS1 markedly inhibited the proliferation of HCT116 by inducing cell cycle arrest. Knockdown of FEZF1-AS1 depletion also led to apoptosis in CRC cells by suppressing the P53 signaling pathway and EMT, thereby reducing their viability, proliferation, migration, and invasion. In summary, this study confirmed that FEZF1-AS1 regulates the growth of junction HCT116 through P53 signaling pathway and inhibiting EMT, providing new insights for the potential therapeutic strategies against CRC.

Hereditary spinocerebellar ataxia (SCA) is a group of genetic neurodegenerative disorders caused by a variety of gene variants. At least 44 types of SCAs have been identified to date, and more than 35 genes and hundreds of variants have been reported that are associated with SCAs. We have investigated a Pakistani consanguineous six-generation family with SCA by using whole-exome sequencing analysis. We identified a reported SCA-associated variant, c.C2687G (p.P896R) in CACNA1A, in only a subgroup of the family, while a c.C262T (p.P88S) variant in ARFIP1 serves as a candidate pathogenic variant in the other subgroup as a possible novel cause of SCA. Our study showed that intra-familial heterogeneity may exist in SCA families and presented a candidate new causative gene for SCA.

Systemic lupus erythematosus is a chronic autoimmune disease that has been associated with human leukocyte antigen G (HLA-G) in previous studies on immunological diseases. This study aimed to investigate the association between three HLA-G gene polymorphisms (rs1632947, rs1233334, and rs371194629) and their impact on HLA-G mRNA expression and soluble HLA-G levels in serum. Genotyping was performed using TaqMan probe PCR. RNA extraction, reverse transcription PCR, and real-time PCR assays were conducted to assess the expression of the HLA-G gene in tissue samples. Soluble HLA-G was measured using enzyme-linked immunosorbent assay in serum. Results show a significant difference in the frequency of the G allele for two 5'-untranslated region (UTR) polymorphisms of the HLA-G gene (rs1632947 and rs1233334) located at positions -964 and -725, respectively, between lupus patients and controls, with p-values of 0.009 and 0.040, respectively. In addition, the study identified the 14 bp insertion allele of the rs371194629 polymorphism located in the 3' UTR of the gene as a risk factor for lupus, with a p-value of 0.001. Our results also indicate that lupus-related alleles may increase the risk of developing the disease by upregulating the expression of HLA-G and increasing soluble HLA-G levels in serum. The findings of the study suggest that the identified genetic variants may play a role in the development of lupus and could be useful in identifying individuals at risk for the disease. These results are important for advancing our understanding of the genetic basis of lupus and may have implications for the development of new treatments and diagnostic tools for the disease.

Exosome-delivered circular RNAs (circRNAs) are recognized as a key mechanism that regulates osteosarcoma (OS) progression. The purpose of this study is to discover the role of a novel circRNA hsa_circ_0000116 from exosomes in OS progression. Transmission electron microscopy, nanoparticle tracking analysis, and western blotting were used to identify the exosomes isolated from two OS cell lines (HOS and MG-63). After coculturing exosomes with OS cells and transfecting hsa_circ_0000116 knockdown vector into OS cells, cell function experiments, including cell counting kit-8, wound healing, and Transwell experiments, were performed to assess the change of OS cell malignant phenotype. In addition, the levels of PI3K/Akt/mTOR and p38/MAPK pathways-associated proteins were measured using western blotting. Exosomes with around 100 nm in diameter were successfully isolated from HOS and MG-63 cells, and promote OS cells to proliferate, migrate, and invade. hsa_circ_0000116 was upregulated in OS-derived exosomes, and silencing hsa_circ_0000116 declined the exosome-induced OS cell malignancy. In addition, inhibiting hsa_circ_0000116 effectively inhibited exosome-mediated activation of PI3K/Akt/mTOR and p38/MAPK pathways. In conclusion, exosomal hsa_circ_0000116 can facilitate OS cell malignancy by inducing the activation of PI3K/Akt/mTOR and p38/MAPK pathways. The findings of this study may identify novel molecular mechanisms driving OS progression and provide novel therapeutic targets for OS.

Amniotic fluid-derived stem cells (AFSCs) represent a promising yet underutilized resource for research and clinical applications. While AFSCs share phenotypic and functional characteristics with stem cells derived from somatic tissues such as bone marrow, adipose tissue, placenta, and umbilical cord, their unique developmental origin grants them several superior qualities. These include enhanced multipotency, tissue-specific genotypic profiles, and the ability to form single-cell colonies. Such features position AFSCs as highly valuable for translational research and tissue engineering. This review seeks to underscore the distinctive attributes of AFSCs, particularly their relevance in developmental research and engineering. By emphasizing these qualities, we aim to stimulate further exploration into their use in patient-specific induced pluripotent stem cells and organoid development, potentially unlocking their full therapeutic potential. The unique capabilities of AFSCs make them an exceptional candidate for advancing regenerative medicine, offering new avenues for treating a variety of conditions that currently have limited therapeutic options.