MicroRNA‐24‐3p (miR‐24‐3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer‐associated fibroblasts (CAFs) can secret exosomes to transfer ...miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF‐derived exosomal miR‐24‐3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF‐derived exosomal miR‐24‐3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR‐24‐3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells. The relationship among HEPH, CDX2 and miR‐24‐3p was verified using ChIP and dual‐luciferase reporter gene assays. Exosomes were isolated from miR‐24‐3p inhibitor–treated CAFs (CAFs‐exo/miR‐24‐3p inhibitor), which were used in combination with gain‐of‐function and loss‐of‐function experiments and MTX treatment. CCK‐8, flow cytometry and colony formation assays were conducted to determine cell viability, apoptosis and colony formation, respectively. Based on the findings, CC tissues and cells presented with high expression of miR‐24‐3p and low expression of HEPH and CDX2. CDX2 was a target gene of miR‐24‐3p and could up‐regulate HEPH. Under MTX treatment, overexpressed CDX2 or HEPH and down‐regulated miR‐24‐3p reduced cell viability and colony formation and elevated cell apoptosis. Furthermore, miR‐24‐3p was transferred into CC cells via CAF‐derived exosomes. CAF‐derived exosomal miR‐24‐3p inhibitor diminished cell viability and colony formation and increased cell apoptosis in vitro and inhibited tumour growth in vivo under MTX treatment. Altogether, CAF‐derived exosomal miR‐24‐3p accelerated resistance of CC cells to MTX by down‐regulating CDX2/HEPH axis.
Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an ...attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP‐qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR‐433, while dual luciferase assay was carried out to confirm the targeting relationship between miR‐433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo‐tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A‐miR‐433‐FXYD3‐PI3K‐AKT axis in the progression of HCC after loss‐ and gain‐function assays. KDM5A p‐p85 and p‐AKT were highly expressed but miR‐433 was down‐regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR‐433 by demethylating H3K4me3 on its promoterregion. miR‐433 negatively targeted FXYD3. Depleting miR‐433 or re‐expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down‐regulated miR‐433 and up‐regulated FXYD3‐PI3K‐AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3‐PI3K‐AKT axis to enhance angiogenesis in HCC by suppressing miR‐433.
Previous evidence has highlighted M2 macrophage regulation of cancer cells via exosome shuttling of microRNAs (miRNAs or miRs). The current study set out to explore the possible role of M2 ...macrophage-derived exosomal miR-155-5p in regard to immune escape of colon cancer cells. Experimental data from quantitative reverse-transcriptase PCR (qRT-PCR) and western blot analysis revealed highly expressed miR-155-5p and interleukin (IL)-6 and poorly expressed ZC3H12B in M2 macrophage-derived exosomes. Additionally, miR-155-5p could be transferred by M2 macrophage-isolated exosomes to colon cancer cells, which targeted ZC3H12B by binding to the 3¢ UTR, as identified by dual luciferase reporter gene. Meanwhile, gain- and loss-of function experimentation on miR-155-5p and ZC3H12B in SW48 and HT29 cells cocultured with M2 macrophage-secreted exosomes demonstrated that miR-155-5p overexpression or ZC3H12B silencing promoted the proliferation and antiapoptosis ability of SW48 and HT29 cells, as well as augmenting the CD3+ T cell proliferation and the proportion of interferon (IFN)-γ+ T cells. Xenograft models confirmed that M2 macrophage-derived exosomal miR-155-5p reduced the ZC3H12B expression to upregulate IL-6, which consequently induced immune escape and tumor formation. Collectively, our findings indicated that M2 macrophage-derived exosomal miR-155-5p can potentially promote the immune escape of colon cancer by impairing ZC3H12B-mediated IL-6 stability reduction, thereby promoting the occurrence and development of colon cancer.
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miR-155-5p was transferred by M2 macrophage-derived exosomes into colon cancer cells, where miR-155-5p targeted ZC3H12B, which in turn negatively regulated the stability of IL-6 mRNA. By this mechanism, miR-155-5p inhibited T cell immune response and thus promoted immune escape in colon cancer.
Xenœstrogens (XEs) are a class of substances that exert estrogenic effects by mimicking or blocking endogenous hormones. The sources, environmental behavior, and fate of typical XEs are described. ...XEs’ adverse developmental, metabolic, and immunological effects are then presented with respect to reproductive functions. The mechanisms underlying XEs’ genomic and nongenomic effects are reviewed. XEs can alter gene transcription by interfering with the functioning of conventional estrogen receptors, but they are also capable of activating multiple kinase signaling pathways that disrupt membrane-associated receptors, such as estrogen receptor alpha-36 (ERα36), estrogen receptor alpha-46 (ERα46), and G protein-coupled receptor 30 (GPR30). This review aims to provide insight into XEs’ environmental effects and to explore the prevention and treatment of their estrogenic effects based on sufficient comprehension of the mechanisms involved.
Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors that are harmful to human health. Increasing evidence has underscored the critical role of the competitive endogenous RNA ...(ceRNA) regulatory networks among various human cancers. However, the complexity and behavior characteristics of the ceRNA network in HCC were still unclear. In this study, we aimed to clarify a phosphatase and tensin homolog (PTEN)-related ceRNA regulatory network and identify potential prognostic markers associated with HCC. The expression profiles of three RNAs (long non-coding RNAs lncRNAs, microRNAs miRNAs, and mRNAs) were extracted from The Cancer Genome Atlas (TCGA) database. The DLEU2L-hsa-miR-100-5p/ hsa-miR-99a-5p-TAOK1 ceRNA network related to the prognosis of HCC was obtained by performing bioinformatics analysis. Importantly, we identified the DLEU2L/TAOK1 axis in the ceRNA by using correlation analysis, and it appeared to become a clinical prognostic model by Cox regression analysis. Furthermore, methylation analyses suggested that the abnormal upregulation of the DLEU2L/TAOK1 axis likely resulted from hypomethylation, and immune infiltration analysis showed that the DLEU2L/TAOK1 axis may have an impact on the changes in the tumor immune microenvironment and the development of HCC. In summary, the current study constructing a ceRNA-based DLEU2L/TAOK1 axis might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC.
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Shi et al. provide evidence that a ceRNA-based DLEU2L/TAOK1 axis has an impact on changes in the tumor immune microenvironment and might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC.
In this study, a novel suspended ceramsite was prepared, which has high strength, optimum density (close to water), and high porosity. The ceramsite was used to feed a moving-bed biofilm reactor ...(MBBR) system with an anaerobic-aerobic (A/O) arrangement to treat petroleum refinery wastewater for simultaneous removal of chemical oxygen demand (COD) and ammonium. The hydraulic retention time (HRT) of the anaerobic-aerobic MBBR system was varied from 72 to 18 h. The anaerobic-aerobic system had a strong tolerance to shock loading. Compared with the professional emission standard of China, the effluent concentrations of COD and NH3-N in the system could satisfy grade I at HRTs of 72 and 36 h, and grade II at HRT of 18 h. The average sludge yield of the anaerobic reactor was estimated to be 0.0575 g suspended solid/g CODremoved. This work demonstrated that the anaerobic-aerobic MBBR system using the suspended ceramsite as bio-carrier could be applied to achieving high wastewater treatment efficiency.
Numerous studies have suggested that dysregulated long noncoding RNAs (lncRNAs) contributed to the development and progression of many cancers. lncRNA OIP5 antisense RNA 1 (OIP5-AS1) has been ...reported to be increased in several cancers. However, the roles of OIP5-AS1 in liver hepatocellular carcinoma (LIHC) remain to be investigated. In this study, we demonstrated that OIP5-AS1 was upregulated in LIHC tissue specimens and its overexpression was associated with the poor survival of patients with LIHC. Furthermore, loss-of function experiments indicated that OIP5-AS1 promoted cell proliferation and inhibited cell apoptosis both in vitro and in vivo. Moreover, binding sites between OIP5-AS1 and hsa-miR-26a-3p as well as between hsa-miR-26a-3p and EPHA2 were confirmed by luciferase assays. Finally, a rescue assay was performed to prove the effect of the OIP5-AS1/hsa-miR-26a-3p/EPHA2 axis on LIHC cell biological behaviors. Based on all of the above findings, our results suggested that OIP5-AS1 promoted LIHC cell proliferation and invasion via regulating the hsa-miR-26a-3p/EPHA2 axis.
To systematically evaluate the whole-transcriptome sequencing data of cholangiocarcinoma (CHOL) to gain more insights into the transcriptomic landscape and molecular mechanism of this cancer, we ...performed whole-transcriptome sequencing based on the tumorous (C) and their corresponding non-tumorous adjacent to the tumors (CP) from eight CHOL patients. Subsequently, differential expression analysis was performed on the C and CP groups, followed by functional interaction prediction analysis to investigate gene-regulatory circuits in CHOL. In addition, The Cancer Genome Atlas (TCGA) for CHOL data was used to validate the results. In total, 2,895 differentially expressed messenger RNAs (dif-mRNAs), 56 differentially expressed microRNAs (dif-miRNAs), 151 differentially expressed long non-coding RNAs (dif-lncRNAs), and 110 differentially expressed circular RNAs (dif-circRNAs) were found in CHOL samples compared with controls. Enrichment analysis on those differentially expressed genes (DEGs) related to miRNA, lncRNA, and circRNA also identified the function of spliceosome. The downregulated hsa-miR-144-3p were significantly enriched in the competing endogenous RNA (ceRNA) complex network, which also included 7 upregulated and 13 downregulated circRNAs, 7 upregulated lncRNAs, and 90 upregulated and 40 downregulated mRNAs. Moreover, most of the DEGs and a few of the miRNAs (such as hsa-miR-144-3p) were successfully validated by TCGA data. The genes involved in RNA splicing and protein degradation processes and miR-144-3p may play fundamental roles in the pathogenesis of CHOL.
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The whole-transcriptome sequencing data of cholangiocarcinoma (CHOL) were systematically evaluated to gain more insights into the transcriptomic landscape and molecular mechanism of this cancer.
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•SUVA254 and HIX are indicators for bioavailability.•Dissolved organic matter over 10 kDa transformed into 0–10 kDa, which improved bioavailability.•The protein-like matter of 0–5 kDa ...is critical for improving bioavailability.•The humic-like matter of 5–100 kDa is essential for improving bioavailability.
In this study, swine wastewater (SW) and cow wastewater (CW) were used for anaerobic digestion (AD). We found the bioavailability of dissolved organic matter (DOM) was affected by the molecular weight ranges and molecular composition during the AD process. The organic substance in the small molecular range (0–5 kDa) accumulated due to a larger molecular fraction (>10 kDa) degradation, which enhanced the bioavailability of the DOM. Moreover, based on the excitation emission matrix-parallel factor (EEM-PARAFAC) analysis, the protein-like component in 0–5 kDa molecular size and humic-like component over 5 kDa are significantly positively correlated with DOM bioavailability. This study indicated that increasing the hydrolysis of larger organic matter and humification degree of molecular weights>5 kDa are critical solutions to improving the bioavailability of DOM. These conclusions can help explain the molecular mechanisms of DOM transformation and the AD process of livestock wastewater.
Abstract
We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent ...non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1.
miR-320b suppresses angiogenesis in lung cancer. miR-320b targets HNF4G and inhibits its expression. HNF4G increases IGF2BP2 expression to promote lung cancer. IGF2BP2 enhances the m6A modification of TK1 to promote lung cancer.
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