Bladder cancer (BCa) is one of the most prevalent cancers of the urinary system worldwide. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) perform a vital function in the ...pathogenesis and progression of BCa. In the current study, we identified a novel lncRNA OXCT1‐AS1 and investigated its role and potential mechanisms in BCa. The microarray results showed the expression of lncRNAs, microRNAs, and messenger RNAs between BCa primary tumor tissues and metastatic lymph nodes were significantly different. The quantitative polymerase chain reaction verification was performed to ensure the reliability of the screening results. The Cell Counting Kit 8 and transwell assay were used to assess the tumor cell proliferation and invasion abilities in vitro, respectively. The dual‐luciferase activity assay was performed to investigate the potential mechanism of competing endogenous RNA network. lncRNA OXCT1‐AS1, which elevated in metastasis lymph node, was significantly upregulated in BCa cell lines compared with SVHUC‐1. We demonstrated OXCT1‐AS1 inhibited miR‐455‐5p to decrease its binding to the JAK1 3′‐untranslated region, which could upregulate the expression of JAK1 at the protein level, thus promoting BCa proliferation and invasion. Therefore, lncRNA OXCT1‐AS1 could act as a potential biomarker and therapeutic target for patients with BCa.
The microarray results showed the expression of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) between bladder cancer (BCa) metastatic lymph nodes and primary tumor tissues were significantly different. lncRNA OXCT1‐AS1, which elevated in metastasis lymph node, was significantly upregulated in BCa cell lines compared with SVHUC‐1. We demonstrated OXCT1‐AS1 inhibited miR‐455‐5p to decrease its binding to the JAK1 3′‐untranslated region (UTR), which could upregulate the expression of JAK1 at the protein level, thus promoting BCa proliferation and invasion.
A rhodium-catalyzed tandem enantioselective C–H silylation/alkene hydrosilylation of dihydrosilanes, which enables the streamlined construction of a wide range of silicon-stereogenic silanes, is ...successfully developed. This process involves a SiH2-steered highly enantioselective C–H silylation to furnish the corresponding desymmetric monohydrosilanes, which are subsequently trapped with alkenes in a stereospecific fashion to build functionally diverse asymmetrically tetrasubstituted silanes. This general strategy combines readily available dihydrosilanes and alkenes to construct various enantioenriched silicon-stereogenic silanes, including 9-silafluorenes, Si-bridged ladder compounds, and benzosilolometallocenes, in a single step with good to excellent yields and enantioselectivities.
The mantle source of the Cenozoic intraplate basalts from the Shuangliao volcanoes in the Songliao Basin in northeastern China (Xu et al., 2012) has been suggested to contain young subducted recycled ...oceanic crust (ROC), whereas the mantle source of the Cenozoic basalts from the nearby Changbaishan volcanoes contain recent and ancient recycled marine sediments (Kuritani et al., 2011). To determine the possible contributions of recycled marine sediments to the mantle source of the Shuangliao Cenozoic basalts, we measured the H2O content in clinopyroxene (cpx) phenocrysts by Fourier transform infrared spectrometry (FTIR) and calculated H2O contents of equilibrated melts using the partition coefficient of H2O between cpx and basaltic melt. Major and trace element compositions measured in the Shuangliao whole rocks are consistent with a previous study by Xu et al. (2012) and display typical HIMU characteristics. The calculated H2O content of the “primary” magmas varies from 0.90 to 3.06wt.%, falling in the range of back-arc basin basalts (BABBs) and island arc basalts (IABs) and it is higher than that of mid-ocean ridge basalts (MORBs) and ocean island basalts (OIBs). The relationships between H2O/Ce and (Ba/Th)n (n denotes normalization to primitive mantle composition), (Nb/La)n and Ce/Pb of the Shuangliao basalts indicate that in addition to ROC with low H2O/Ce and high (Nb/La)n, recycled marine sediments with high H2O/Ce, (Ba/Th)n and low Ce/Pb and a normal depleted mantle (DMM) component should also be involved in the magma source. In addition, the mantle source of the later (~43Ma) basalts should contain more recycled marine sediments than that of the earlier (~51Ma) basalts.
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•Water contents of the Shuangliao Cenozoic basalts of NE China have been estimated.•DMM, ROC and recycled sediments have been involved in the mantle source.•The relative contribution of the three components has changed with time.
Several studies suggest that metformin has the potential effect of reducing cancer risk. However, its survival benefit in patients with colorectal cancer (CRC) and diabetes is unknown. The aim of our ...study is to address the effect of metformin on outcomes for CRC based on a systematic review and meta-analysis.
We searched EMBASE and MEDLINE databases from inception through August, 2013, using search terms related to metformin, diabetes, colorectal cancer, and prognostic outcome. The outcome measures were hazard ratios (HRs) with 95% CIs comparing CRC survival in diabetic patients using metformin and without using metformin. The primary end points were overall survival (OS) and CRC specific survival (CS). A total of six cohort studies including 2,461 patients met full eligibility criteria. The pooled HR favoring metformin users was 0.56 for OS (95% CI, 0.41 to 0.77) and 0.66 for CRC-specific survival (95% CI, 0.50 to 0.87). Thus metformin therapy reduced the risk of all cause of death by 44% and the risk of CRC specific death by 34% in CRC patients compared to those in non-users. However, evidence of heterogeneity and possible publication bias was noted for OS.
Patients with CRC and diabetes treated with metformin appear to have an improved survival outcome. Prospective study should be warranted to examine the association between metformin exposure intensity as well as some other confounding variables and survival outcome in diabetic CRC patients.
AIM:To investigate the mechanism by which miR-204-3p inhibits the growth of hepatocellular carcinoma(hCC)tumor endothelial cells(TECs).METHODS:Flow cytometry was used to identify hCCTECs and analyze ...their purity.Differentially expressed miRNAs in hCC TECs as compared to normal hepatic sinusoidal endothelial cells(hSECs)were examined using the hmiOA v4 human miRNA OneArray?microarray.miR-204-3p showed the most significant decrease in expression and was further studied.Over-expression of miR-204-3p was achieved using lentiviral transduction into TECs of hCC.The biological changes in hCC TECs before and after transduction were detected using MTT and apoptosis assays.The association between miR-204-3p and fibronectin 1(FN1)was determined using the dual luciferase activity assay.Changes in FN1protein expression before and after transduction were detected using Western blot analysis.RESULTS:Microarray results showed that compared to normal hSECs,15 miRNAs were differentially expressed in hCC TECs,including 6 miRNAs with increased expression and 9 miRNAs with decreased expression.Among them,miR-204-3p showed the most significant decrease in expression(log2=-1.233477,P=0.000307).Over-expression of miR-204-3p in hCC TECs via lentiviral transduction significantly inhibited the proliferation of hCC TECs and promoted apoptosis.Results from the dual luciferase activity experiment showed that the luciferase intensity in the wild type FN1 group was significantly inhibited(P<0.05),while that in the mutant FN1 group was not obviously affected.This observation indicated that FN1 was one of the potential targets of miR-204-3p.After over-expression of miR-204-3p in hCC TECs,Western blot analysis showed that the expression of FN1 protein was significantly inhibited.CONCLUSION:MiR-204-3p acts on its potential target gene,FN1,and inhibits its expression,thus blocking the adhesion function of FN1 in promoting the growth of TECs.
The prognostic value of the tumor burden score (TBS) in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remains unknown. This study aimed to investigate the impact of TBS on ...long-term outcomes after surgery.
Patients who underwent radical-intent resection between June 2013 and December 2019 were retrospectively reviewed. Kaplan-Meier curves were used to analyze patient survival, and disease-free survival (DFS) and overall survival (OS) were examined in relation to TBS.
A total of 178 patients were included in this study, with 119 in the training cohort and 59 in the validation cohort. Kaplan-Meier curves showed that TBS was a strong prognostic indicator in patients with cHCC-CCA. Elevated TBS was associated with poorer DFS and OS (both P-value < 0.001) and was identified as an independent prognostic indicator. In addition, the prognostic value of TBS outperformed tumor size and number alone, microvascular invasion, and lymph node invasion. The prognostic significance of TBS was confirmed by the internal validation cohort.
The present study suggested the significance of tumor morphology in assessing the prognosis of patients with cHCC-CCA who undergoing curative resection. The TBS is a promising prognostic index in patients with cHCC-CCA. Elevated TBS was related to a lower long-term survival rate and was identified as an independent risk factor for poor DFS and OS. Further research is needed to verify our results.
To investigate the effects of CCL21/CCR7 on the proliferation, migration, and invasion of T24 cells and the possible associated mechanisms: expression of MMP-2 and MMP-9, and regulation of BCL-2 and ...BAX proteins.
T24 cells received corresponding treatments including vehicle control, antibody (20 ng/mL CCR7 antibody and 50 ng/ml CCL21), and 50, 100, and 200 ng/ml CCL21. Proliferation was evaluated by MTT assay; cell migration and invasion were assayed using a transwell chamber. Cell apoptosis was induced by Adriamycin (ADM). The rate of cell apoptosis was examined by flow cytometry using annexin V-FITC/PI staining. Western-blot was used to analyze MMP-2 and MMP-9 and BCL-2 and BAX proteins.
CCL21 promoted T24 cell proliferation in concentration-dependent manner with that 200 ng/mL induced the largest amount of proliferation. Significant differences of cell migration were found between CCL21treatment groups and the control group in both the migration and invasion studies (P < 0.001 for all). The expressions of MMP-2 and MMP-9 proteins were significantly increased after CCL21 treatment (p < 0.05 for all). Protein expression of Bcl-21 follows an ascending trend while the expression of Bax follows a descending trend as the concentration of CCL21 increases. No difference was found between the control group and antibody group for all assessments.
CCL21/CCR7 promoted T24 cell proliferation and enhanced its migration and invasion via the increased expression of MMP-2 and MMP-9. CCL21/CCR7 had antiapoptotic activities on T24 cells via regulation of Bcl-2 and Bax proteins. CCL21/CCR7 may promote bladder cancer development and metastasis.
To explore the relationship between the genotype and renal phenotype in a Chinese cohort and guide clinical decision-making for treating tuberous sclerosis complex (TSC). We reviewed 173 patients ...with definite TSC at three centers in China from September 2014 to September 2020. All the patients underwent TSC1 and TSC2 genetic testing as well as renal phenotypic evaluation. All analyses were performed using the SPSS software, version 19.0, with a cut-off P value of 0.05 considered statistically significant. We identified variants in 93% (161/173) cases, including 16% TSC1 and 77% TSC2 variants. Analysis of the relationship between the genotype and renal phenotype, revealed that those with TSC2 variants were more likely to develop severe renal AML (> 4) (P = 0.044). In terms of treatment, TSC2 variants were more likely to undergo nephrectomy/partial nephrectomy (P = 0.036) and receive mTOR medication such as everolimus (P < 0.001). However, there was no significant difference between the two groups in terms of their response to the everolimus treatment.
Abstract
Circular RNAs (circRNAs), which exert critical functions in the regulation of transcriptional and post-transcriptional gene expression, are found in mammalian cells but their functions in ...mammalian preimplantation embryo development remain poorly understood. Here, we showed that circKDM5B mediated miRNA-128 (miR-128) to regulate porcine early embryo development. We screened circRNAs potentially expressed in porcine embryos through an integrated analysis of sequencing data from mouse and human embryos, as well as porcine oocytes. An authentic circRNA originating from histone demethylase KDM5B (referred to as circKDM5B) was abundantly expressed in porcine embryos. Functional studies revealed that circKDM5B knockdown not only significantly reduced blastocyst formation but also decreased the number of total cells and trophectoderm (TE) cells. Moreover, the knockdown of circKDM5B resulted in the disturbance of tight junction assembly and impaired paracellular sealing within the TE epithelium. Mechanistically, miR-128 inhibitor injection could rescue the early development of circKDM5B knockdown embryos. Taken together, the findings revealed that circKDM5B functions as a miR-128 sponge, thereby facilitating early embryonic development in pigs through the modulation of gene expression linked to tight junction assembly.
The Pacific plate since the Mesozoic is subducting into the mantle beneath the eastern Asia, and the involved recycled crustal material has greatly affected the mantle geochemistry. However, the ...initial timing of the subduction remains controversial, partly due to the insufficient understanding of the geochemical evolution of the Mesozoic mantle. The present study provides new constraints on this aspect using whole-rock and olivine phenocryst compositions of Mesozoic basalts from the Jitai Basin of South China, which is part of the eastern Asian volcanic belt. Multiple OIB-type basalts outcrop in the Jitai Basin ranging in age from 168 Ma to 90 Ma. In comparison with normal mantle, these basalts exhibit higher (87Sr/86Sr)i, Ba/Th, Nb/La and lower εNd(t). Their olivine phenocrysts display high Ni contents and low Mn and Ca contents. Together, these indicators suggest that components of recycled oceanic crust were involved in the mantle source of the basalts. Moreover, combined with the observations from the Hebu basalts, from 168 Ma to 63 Ma, it shows that the component of the recycled oceanic crust was continuously supplied to the mantle source of the Jitai Basin basalts. Considering that the Jitai Basin basalts have whole-rock and olivine phenocryst compositions similar to those of the Cenozoic basalts from eastern China, which were originated from a stagnant Pacific plate in the mantle transition zone, we propose that the same origin may be the best candidate for the components of recycled oceanic crust in the mantle source of the Jitai Basin basalts. Finally, it is possible to estimate that the westward subduction of the Pacific plate probably started in an earlier stage.
•Recycled oceanic slab was identified in the mantle source of the Jitai Basin basalts.•Oceanic crust was involved in the mantle source of the Jitai Basin basalts since 168Ma.•The Pacific plate may have had an impact on South China since the middle Jurassic.
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