Search

Simple Summary: Breast cancer is a disease that begins in the cells of the breast. Although it is most common in women, it can also occur in men, though this is rare. Early detection and treatment are crucial to improving outcomes and survival rates. Risk factors include age, family history, certain gene mutations, prior history of breast cancer, exposure to estrogen, and lifestyle habits like alcohol consumption and inactivity. Symptoms include changes in the skin on the breast, such as dimpling, lumps or thickening, changes in size or shape, and discharge from the nipple. Diagnosis is often made through a clinical breast exam, mammogram, biopsy, and possibly additional imaging tests. Treatment options include surgery, chemotherapy, radiation therapy, hormone therapy, and targeted therapy. The choice of treatment method depends on the stage and characteristics of cancer. Breast cancer is considered the solid tumor most sensitive to chemotherapy. However, it can become resistant to various chemotherapeutic drugs, including doxorubicin, which triggers cell death by intercalation between DNA bases, free radical formation, and topoisomerase II inhibition. When drug resistance develops, several miRNAs are dysregulated, suggesting that miRNAs may play a significant role in resistance formation. In the current study, we investigated how doxorubicin sensitivity of breast cancer cells is affected by miR-153-3p and its target gene. The MTT method was used to determine the chemo-sensitizing effect of miR-153-3p on doxorubicin in MCF-7 and MDA-MB-231 cell lines. Results of Western blot and dual luciferase confirmed that miR-153-3p targets KIF20A and decreases its expression. Transwell and flow cytometry experiments showed that miR-153-3p and doxorubicin together had higher effects on MCF-7 and MDA-MB-231 cell proliferation, migration, and invasion, as well as increasing apoptosis and arresting cells in the G1 phase. Proteins related to apoptosis and the cell cycle exhibited the same tendency. Intracellular vesicle formation was inhibited and RAB26 was also downregulated by treatment with miR-153-3p alone or in combination with doxorubicin. Doxorubicin's ability to suppress tumors may be enhanced by miR-153-3p, according to in vivo studies. According to our findings, miR-153-3p has a direct effect on KIF20A and may regulate the formation of intracellular vesicles, which in turn makes breast cancer cells more susceptible to doxorubicin. [ABSTRACT FROM AUTHOR]

Acute exacerbation chronic obstructive pulmonary disease (AECOPD) has a high mortality rate. However, there is no efficiency biomarker for diagnosing AECOPD. The purpose of this study was to find biomarkers that can quickly and accurately diagnose AECOPD.45 normal controls (NC), 42 patients with stable COPD (SCOPD), and 66 patients with AECOPD were enrolled in our study. Serum exosomes were isolated by ultracentrifuge and verified by morphology and specific biomarkers. Fluorescent quantitation polymerase chain reaction (qRT-PCR) was used to detect the expression of micro RNAs (miRNAs), including miR-660-5p, miR-1258, miR-182-3p, miR-148a-3p, miR-27a-5p and miR-497-5p in serum exosomes and serum. Logistic regression and machine learning methods were used to constructed the diagnostic models of AECOPD. The levels of miR-1258 in the patients with AECOPD were higher than other groups (p < 0.001). The ability of exosomal miR-1258 (AUC = 0.851) to identify AECOPD from SCOPD was superior to other biomarkers, and the combination of exosomal miR-1258 and NLR can increase the AUC to 0.944, with a sensitivity of 81.82%, and specificity of 97.62%. The cross-validation of the models displayed that the logistic regression model based on exosomal miR-1258, NLR and neutrophil count had the best accuracy (0.880) in diagnosing AECOPD from SCOPD. The three most correlated biomarkers with serum exosome miR-1258 were neutrophil count (r = 0.57, p < 0.001), WBC (r = 0.50, p < 0.001) and serum miR-1258 (r = 0.33, p < 0.001). In conclusion, serum exosomal miR-1258 is associated with inflammation, and can be used as a valuable and reliable biomarker for the diagnosis of AECOPD, and the establishment of diagnostic model based on miR-1258, NLR and neutrophils count can help to improving the accuracy of AECOPD diagnosis. [ABSTRACT FROM AUTHOR]

In mammals, ovarian function is dependent on the primordial follicle pool and the rate of primordial follicle activation determines a female's reproductive lifespan. Ovarian ageing is characterised by chronic low‐grade inflammation with accelerated depletion of primordial follicles and deterioration of oocyte quality. Macrophages (Mφs) play critical roles in multiple aspects of ovarian functions; however, it remains unclear whether Mφs modulate the primordial follicle pool and what is their role in ovarian ageing. Here, by using super‐ or naturally ovulated mouse models, we demonstrated for the first time that ovulation‐induced local inflammation acted as the driver for selective activation of surrounding primordial follicles in each estrous cycle. This finding was related to infiltrating Mφs in ovulatory follicles and the dynamic changes of the two polarised Mφs, M1 and M2 Mφs, during the process. Further studies on newborn ovaries cocultured with different subtypes of Mφs demonstrated the stimulatory effect of M1 Mφs on primordial follicles, whereas M2 Mφs maintained follicles in a dormant state. The underlying mechanism was associated with the differential regulation of the Phosphatidylinositol 3‐kinase/Mechanistic target of rapamycin (PI3K/mTOR) signaling pathway through secreted extracellular vesicles (EVs) and the containing specific miRNAs miR‐107 (M1 Mφs) and miR‐99a‐5p (M2 Mφs). In aged mice, the intravenous injection of M2‐EVs improved ovarian function and ameliorated the inflammatory microenvironment within the ovary. Thus, based on the anti‐ageing effects of M2 Mφs in old mice, M2‐EVs may represent a new approach to improve inflammation‐related infertility in women. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) have emerged as key players in various human biological processes, including tumorigenesis. Here, we investigated the roles of miR-375 in the pathogenesis of oral squamous cell carcinoma (OSCC). Methods: We performed quantitative real-time PCR (qRT-PCR) to detect miR-375 expression in OSCC tissues and corresponding normal oral epithelial tissues and analyze the correlation of miR-375 expression with OSCC metastasis and patient's survival. Then, the effects of miR-375 expression on proliferation, cell cycle, apoptosis and radiosensitivity in OSCC cells were determined by using MTT, flow cytometry and clonogenic survival assays. A dual-luciferase reporter assay was performed to test whether miR-375 binds to the 3'-untranslated region (3'-UTR) of target mRNA. Results: The expression level of miR-375 in OSCC tissues was significantly lower than that in normal oral epithelial tissues, and low miR-375 expression was correlated with higher incidence of lymph node metastasis and poor survival of OSCC patients. Upregulation of miR-375 significantly inhibits growth, induces cell cycle arrest in G0/G1 phase, increases apoptosis and enhances radiosensitivity in OSCC cells. Analysis of luciferase activity demonstrated that miR-375 binds to the 3'-UTR of insulin like growth factor 1 receptor (IGF-1R). Small interfering RNA (shRNA)-mediated IGF-1R knockdown mimics the effects of miR-375 upregulation, while overexpression of IGF-1R partially reverses those effects in OSCC cells. Conclusion: It was obviously demonstrated that miRNA-375 inhibits growth and enhances radiosensitivity in OSCC cells by targeting IGF-1R, suggesting that miR-375 may be a potential therapeutic target for OSCC patients. [ABSTRACT FROM AUTHOR]

Rehmannia glutinosa, a traditional Chinese medicine herb, is unable to grow normally in a soil where the same species has recently been cultivated. The biological basis of this so called “replanting disease” is unknown, but it may involve the action of microRNAs (miRNAs), which are known to be important regulators of plant growth and development. High throughput Solexa/Illumina sequencing was used to generate a transcript library of the R. glutinosa transcriptome and degradome in order to identify possible miRNAs and their targets implicated in the replanting disease. A total of 87,665 unigenes and 589 miRNA families (17 of which have not been identified in plants to date) was identified from the libraries made from a first year (FP) and a second year (SP) crop. A comparison between the FP and SP miRNAs showed that the abundance of eight of the novel and 295 of the known miRNA families differed between the FP and SP plants. Sequencing of the degradome sampled from FP and SP plants led to the identification of 165 transcript targets of 85 of the differentially abundant miRNA families. The interaction of some of these miRNAs with their target(s) is likely to form an important part of the molecular basis of the replanting disease of R. glutinosa. [ABSTRACT FROM AUTHOR]

Background: The present study attempted to identify potential key genes and miRNAs of dyslipidemia in obese, and to investigate the possible mechanisms associated with them.Methods: The microarray data of GSE66676 were downloaded, including 67 obese samples from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network (WGCNA) analysis was performed using WGCNA package and grey60 module was considered as the highest correlation. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for this module were performed by clusterProfiler and DOSE package. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using molecular complex detection.Results: Collagen type I alpha 1 chain gene (COL1A1) had the best significant meaning. After bioinformatic analysis, we identified four miRNAs (hsa-miR-3659, hsa-miR-4658, hsa-miR151a-5p and hsa-miR-151b) which can bind SNPs in 3'UTR in COL1A1. After validation with RT-qPCR, only two miRNAs (hsa-miR-3659 and hsa-miR151a-5p) had statistical significance.Conclusions: The area of 0.806 for miR-3659 and 0.769 for miR-151a-5p under the ROC curve (AUC) may have good diagnostic value for dyslipidemia. Circulating miR-3659 may be a potential biomarker of dyslipidemia in patients with obesity. [ABSTRACT FROM AUTHOR]