Proctorbegum2896

In summary, M2 macrophage-derived exosomes transferred lncRNA AFAP1-AS1 to downregulate miR-26a and upregulate ATF2, thus promoting the invasion and metastasis of EC. Targeting M2 macrophages and the lncRNA AFAP1-AS1/miR-26a/ATF2 signaling axis represents a potential therapeutic strategy for EC.Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are dysregulated in diverse tumors and take a pivotal role in modulating biological processes. In our study, a decreased expression level of LINC00675 in gastric cancer (GC) was first determined by data from The Cancer Genome Atlas (TCGA) and was identified using specimens from GC patients. Then, in vitro and in vivo functional experiments elaborated that LINC00675 could suppress cell proliferation and migration in GC. Multiple differentially expressed genes (DEGs) in LINC00675-overexpressing cells were identified through RNA sequencing analysis. An RNA-binding protein immunoprecipitation (RIP) assay was conducted to reveal that LINC00675 competitively bound with lysine-specific demethylase 1 (LSD1). MEK inhibitor cancer A coimmunoprecipitation (coIP) assay indicated that LINC00675 overexpression may strengthen the binding of LSD1 and H3K4me2, whereas the chromatin immunoprecipitation (ChIP) assay results verified lower expression of H3K4me2 at the sprouty homolog 4 (SPRY4) promoter region. Together, our research identified that LINC00675 was remarkably downregulated in GC tissues and cells relative to nontumor tissues and cells. LINC00675 could repress GC tumorigenesis and metastasis via competitively binding with LSD1 and intensifying the binding of LSD1 and its target H3K4me2. Importantly, this contributed to attenuated binding of H3K4me2 at the promoter region of oncogene SPRY4 and suppressed SPRY4 transcription, thus suppressing GC cell proliferation and migration.Hepatocellular carcinoma (HCC), one of the most aggressive malignancies, ranks as the fourth leading cause of cancer-related deaths worldwide. Emerging evidence indicates that RNA N6-methyladenosine (m6A) plays a critical role in tumor progression. However, the biological function of YTHDF1 in HCC remains unclear. Here, we found that YTHDF1 expression was strikingly elevated in HCC tissues and cell lines and significantly associated with prognosis of HCC patients. Moreover, YTHDF1 expression was transcriptionally regulated by USF1 and c-MYC in HCC. Functional studies showed that YTHDF1 can promote HCC cell proliferation and metastasis both in vitro and in vivo. Multi-omics analysis revealed that YTHDF1 can accelerate the translational output of FZD5 mRNA in an m6A-dependent manner and function as an oncogene through the WNT/β-catenin pathway. Taken together, our study revealed an essential role of YTHDF1 in the progression of HCC cells, which indicated that targeting YTHDF1 may be a potential therapeutic strategy in HCC.[This corrects the article DOI 10.1016/j.omtn.2020.05.019.].As one of the widely occurring RNA modifications, 5-methyluridine (m5U) has recently been shown to play critical roles in various biological functions and disease pathogenesis, such as under stress response and during breast cancer development. Precise identification of m5U sites on RNA is vital for the understanding of the regulatory mechanisms of RNA life. We present here m5UPred, the first web server for in silico identification of m5U sites from the primary sequences of RNA. Built upon the support vector machine (SVM) algorithm and the biochemical encoding scheme, m5UPred achieved reasonable prediction performance with the area under the receiver operating characteristic curve (AUC) greater than 0.954 by 5-fold cross-validation and independent testing datasets. To critically test and validate the performance of our newly proposed predictor, the experimentally validated m5U sites were further separated by high-throughput sequencing techniques (miCLIP-Seq and FICC-Seq) and cell types (HEK293 and HAP1). When tested on cross-technique and cross-cell-type validation using independent datasets, m5UPred achieved an average AUC of 0.922 and 0.926 under mature mRNA mode, respectively, showing reasonable accuracy and reliability. The m5UPred web server is freely accessible now and it should make a useful tool for the researchers who are interested in m5U RNA modification.Polycystic ovary syndrome (PCOS), characterized by the dysfunction of endocrine metabolism, is a common disease among women. Insulin (INS) resistance (IR) is considered as an obstruction to effective PCOS treatment. Here, we aimed to explore the mechanism by which microRNA-222 (miR-222) affects IR in PCOS via Pten. Quantitative reverse transcription-polymerase chain reaction and western blot assays indicated that miR-222 expression was higher in the peripheral blood of PCOS patients with IR than in PCOS patients without IR, while Pten expression was lower. Further mechanistic analysis identified Pten as a target gene of miR-222. Moreover, PCOS rat models were established through the administration of dehydroepiandrosterone and were subsequently treated with miR-222 agomir, miR-222 antagomir, or Pten overexpression plasmid. The inhibition of miR-222 improved ovarian morphology, enhanced the production of serum sex hormones (follicle-stimulating hormone [FSH], luteotropic hormone [LH], estradiol 2 [E2], prolactin [PRL], and testosterone [T]), increased the levels of glucose metabolism indicators (homeostasis model of assessment for IR [HOMA-IR], blood glucose [BG]120min, and INS120min), and reduced the production of progesterone in the PCOS rats. Notably, miR-222 downregulation resulted in the inactivation of the mitogen-activated protein kinase (MAPK)/ERK pathway by upregulating Pten. Collectively, miR-222 inhibition might reduce IR in PCOS by inactivating the MAPK/ERK pathway and elevating Pten expression, which indicates miR-222 as a promising target for PCOS treatment.Skeletal muscle is an important metabolic organ of the body, and impaired skeletal muscle differentiation can result in a wide range of metabolic diseases. It has been shown that microRNAs (miRNAs) play an important role in skeletal muscle differentiation. The aim of this study was to investigate the role of mmu-miR-324-5p in the differentiation of C2C12 myoblasts and lipid droplet deposition in myotubes for future targeted therapies. We found that mmu-miR-324-5p was highly expressed in mouse skeletal muscle. Overexpression of miR-324-5p significantly inhibited C2C12 myoblast differentiation while promoting oleate-induced lipid accumulation and β-oxidation in C2C12 myoblasts. Conversely, inhibition of mmu-miR-324-5p promoted C2C12 myoblast differentiation and inhibited lipid deposition in myotubes. Mechanistically, mmu-miR-324-5p negatively regulated the expression of long non-coding Dum (lncDum) and peptidase M20 domain containing 1 (Pm20d1) in C2C12 myoblasts. Reduced lncDum expression was associated with a significant decrease in the expression of myogenesis-related genes.