Powerfriedrichsen9579

Importantly, the chromatin exhibited a double looping manner that facilitated sense-eRNA to promoter and antisense-eRNA to gene-ending region in cis. Depletion of antisense eRNA impaired its neighbor mRNA expression, cancer growth and invasion. The expressions of antisense eRNA were correlated with biochemical recurrence and clinical marker PSA's levels in patients' tissues. Conclusions The findings indicated that antisense eRNA was a functional RNA and may be a novel target that when suppressed improved prostate cancer therapy and diagnosis. ZINC05007751 chemical structure New chromatin interaction among enhancer, promoter and gene-ending region might provide new insight into the spatiotemporal mechanism of the gene transcription and acting of bi-directional eRNAs.Rationale Glioma stem-like cells (GSCs) contribute to temozolomide (TMZ) resistance in gliomas, although the mechanisms have not been delineated. MethodsIn vitro functional experiments (colony formation assay, flow cytometric analysis, TUNEL assay) were used to assess the ability of extracellular vesicles (EVs) from hypoxic GSCs to promote TMZ resistance in glioblastoma (GBM) cells. RNA sequencing and quantitative Reverse Transcription-PCR were employed to identify the functional miRNA in hypoxic EVs. Chromatin immunoprecipitation assays were performed to analyze the transcriptional regulation of miRNAs by HIF1α and STAT3. RIP and RNA pull-down assays were used to validate the hnRNPA2B1-mediated packaging of miRNA into EVs. The function of EV miR-30b-3p from hypoxic GSCs was verified by in vivo experiments and analysis of clinical samples. Results Hypoxic GSC-derived EVs exerted a greater effect on GBM chemoresistance than those from normoxic GSCs. The miRNA profiling revealed that miR-30b-3p was significantly upregulated in the EVs from hypoxic GSCs. Further, HIF1α and STAT3 transcriptionally induced miR-30b-3p expression. RNA immunoprecipitation and RNA-pull down assays revealed that binding of miR-30b-3p with hnRNPA2B1 facilitated its transfer into EVs. EV-packaged miR-30b-3p (EV-miR-30b-3p) directly targeted RHOB, resulting in decreased apoptosis and increased proliferation in vitro and in vivo. Our results provided evidence that miR-30b-3p in CSF could be a potential biomarker predicting resistance to TMZ. Conclusion Our findings indicated that targeting EV-miR-30b-3p could provide a potential treatment strategy for GBM.Pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), remains a fatal disease with few efficacious treatments. The Hippo signaling pathway, an evolutionarily conserved signaling module, plays critical roles in tissue homeostasis, organ size control and tumorigenesis. The transcriptional coactivator yes-associated protein (YAP), a major downstream effector of the Hippo pathway, is associated with various human cancers including PDAC. Considering its importance in cancer, YAP is emerging as a promising therapeutic target. In this review, we summarize the current understanding of the oncogenic role and regulatory mechanism of YAP in PDAC, and the potential therapeutic strategies targeting YAP.Estrogen and estrogen receptor (ER)-regulated gene transcriptional events have been well known to be involved in ER-positive breast carcinogenesis. Meanwhile, circular RNAs (circRNAs) are emerging as a new family of functional non-coding RNAs (ncRNAs) with implications in a variety of pathological processes, such as cancer. However, the estrogen-regulated circRNA program and the function of such program remain uncharacterized. Methods CircRNA sequencing (circRNA-seq) was performed to identify circRNAs induced by estrogen, and cell proliferation, colony formation, wound healing, transwell and tumor xenograft experiments were applied to examine the function of estrogen-induced circRNA, circPGR. RNA sequencing (RNA-seq) and ceRNA network analysis wereperformed to identify circPGR's target genes and the microRNA (miRNA) bound to circPGR. Anti-sense oligonucleotide (ASO) was used to assess circPGR's effects on ER-positive breast cancer cell growth. Results Genome-wide circRNA profiling by circRNA sequencing (circRse estrogen-induced circRNAs were required for ER-positive breast cancer cell growth, providing a new class of therapeutic targets for ER-positive breast cancer.Development of a powerful sensitization system to alleviate radioresistance for enhanced tumor radiotherapy (RT) remains to be explored. Herein, we present a unique dual-mode endogenous and exogenous nanosensitizer based on dendrimer-entrapped gold nanoparticles (Au DENPs) to realize enhanced tumor RT. Methods Generation 5 poly(amidoamine) dendrimers partially modified with 1,3-propanesultone were used for templated synthesis of Au NPs, and the created zwitterionic Au DENPs were adopted for serum-enhanced delivery of siRNA to lead to the knockdown of hypoxia-inducible factor-1α (HIF-1α) protein and downstream genes to relieve tumor invasion. The Au DENPs/siRNA polyplexes were also used for dual-mode endogenous and exogenous sensitization of tumor RT in vivo. Results Due to the dual-mode endogenous sensitization through HIF-1α gene silencing and the exogenous sensitization through the existing Au component, enhanced RT of cancer cells in vitro and a tumor model in vivo can be realized, which was confirmed by enhanced cytotoxic reactive oxygen species (ROS) generation in vitro and double-strand DNA damage verified from the γ-H2AX protein expression in tumor cells in vivo. By integrating the advantages of HIF-1α gene silencing-induced downregulation of downstream genes and the dual-mode sensitization-enhanced RT, simultaneous inhibition of primary tumors and metastasis can be readily realized. Conclusions The developed zwitterionic Au DENPs may be used as a promising platform for dual-mode endogenously and exogenously sensitized RT of other tumor types.Rationale Reactive oxygen species (ROS) burst from mitochondrial complex I is considered the critical cause of ischemia/reperfusion (I/R) injury. Ginsenoside Rb1 has been reported to protect the heart against I/R injury; however, the underlying mechanism remains unclear. This work aimed to investigate if ginsenoside Rb1 attenuates cardiac I/R injury by inhibiting ROS production from mitochondrial complex I. Methods In in vivo experiments, mice were given ginsenoside Rb1 and then subjected to I/R injury. Mitochondrial ROS levels in the heart were determined using the mitochondrial-targeted probe MitoB. Mitochondrial proteins were used for TMT-based quantitative proteomic analysis. In in vitro experiments, adult mouse cardiomyocytes were pretreated with ginsenoside Rb1 and then subjected to hypoxia and reoxygenation insult. Mitochondrial ROS, NADH dehydrogenase activity, and conformational changes of mitochondrial complex I were analyzed. Results Ginsenoside Rb1 decreased mitochondrial ROS production, reduced myocardial infarct size, preserved cardiac function, and limited cardiac fibrosis.