Long noncoding RNA (lncRNA) have critical roles in various pathophysiological processes, and are frequently dysregulated in many diseases, particularly in cancer. The lncRNA glypican 3 antisense ...transcript 1 (GPC3‐AS1) has been reported to be a potential biomarker for hepatocellular carcinoma (HCC) screening. However, the exact biological functions of GPC3‐AS1 in HCC, and its roles and regulation mechanisms regarding GPC3 are still unknown. In this study, we observed a significant upregulation of GPC3‐AS1 in HCC. Increased expression of GPC3‐AS1 was associated with α‐fetoprotein, tumor size, microvascular invasion, encapsulation, Barcelona Clinic Liver Cancer stage, and worse prognosis of HCC patients. Furthermore, we found that GPC3‐AS1 physically associated with P300/CBP‐associated factor and recruited it to the GPC3 gene body region, consequently inducing an increase in euchromatic histone marks and activating GPC3 transcription. GPC3‐AS1 expression was strongly correlated with GPC3 in HCC tissues. Gain‐of‐function and loss‐of‐function analyses showed that GPC3‐AS1 overexpression enhanced HCC cell proliferation and migration in vitro and xenograft tumor growth in vivo. GPC3‐AS1 knockdown inhibited HCC cell proliferation and migration. Moreover, the effects of GPC3‐AS1 on HCC cell proliferation and migration were dependent on the upregulation of GPC3. Collectively, our studies indicate that GPC3‐AS1 significantly promotes HCC progression via epigenetically activating GPC3, and identifies GPC3‐AS1 as a potential therapeutic target for HCC.
The long noncoding RNA GPC3‐AS1 is significantly upregulated in hepatocellular carcinoma (HCC) and indicates poor prognosis of HCC patients. GPC3‐AS1 physically associates with P300/CBP‐associated factor (PCAF) and recruits it to the GPC3 gene body region, consequently inducing an increase in euchromatic histone marks and activating GPC3 transcription. GPC3‐AS1 overexpression enhances HCC cell proliferation and migration in vitro and xenograft tumour growth in vivo.
A series of well‐defined (NHC)Pd(N–heterocyclic carboxylate)(OAc) complexes (N–heterocyclic carboxylate = pyridine‐2‐carboxylate, quinoline‐2‐carboxylate and isoquinoline‐1‐carboxylate) were ...synthesized and fully characterized by NMR spectra, HR‐MS and X‐ray single crystal diffraction. The obtained complexes were then used for direct C2‐arylation of free (NH)‐indoles with arylsulfonyl hydrazides. With low catalyst loading, all complexes exhibited high catalytic activities for the arylation reactions.
A series of well‐defined (NHC)Pd(N–heterocyclic carboxylate)(OAc) complexes were synthesized and fully characterized by X‐ray single crystal diffraction. The obtained complexes were then used for direct C2‐arylation of free (NH)‐indoles with arylsulfonyl hydrazides.
This study aimed to explore the prevalence of Toxoplasma gondii (T. gondii) among patients in Guangzhou city, South China, and to identify susceptible patient populations and analyze the causes of ...infection differences.
From May 2020 to May 2022, a total of 637 sera were collected from patients, and 205 sera were collected from health participants as health control. All sera were examined by colloidal gold kits to detect the positivity of antibodies against T. gondii. And the positivity of antibodies in sera was confirmed with ARCHITECT i2000SR system.
The prevalence of T. gondii infection in patients was 7.06% (45/637), which was lower than the prevalence in health participants 4.88% (10/205). Among patients, 34 (5.34%) were positive only for IgG, 10 (1.57%) were only for IgM, and 1 (0.16%) was positive for both IgG and IgM. There was a significant difference in prevalence between male and female patients, but not among different age groups or diseases groups. The prevalence of T. gondii infection in diseases groups varied. The prevalence was relatively high in patients with the disorders of thyroid gland and the malignant neoplasms of digestive organs, which suggests that caution should be taken to avoid T. gondii infection in these patients. Surprisingly, the prevalence was quite low in diffuse Large B-cell Lymphoma (DLBC) patients. This may be due to the overexpression of TNF-α in tumor tissues of DLBC patients and the higher protein level of TNF-α in sera of DLBC patients.
This study provides a systematic exploration of the prevalence of T. gondii infection in patients in a tertiary hospital. Our data contributes to a better understanding of the epidemic investigation of T. gondii among patients in South China, which can help the prevention and treatment of the disease caused by T. gondii infection.
Accumulating evidences showed that aberrantly expressed long noncoding RNAs (lncRNAs) have critical roles in many cancers. However, the expression and roles of a poorly studied lncRNA PCNA-AS1 in ...non-small-cell lung cancer (NSCLC) remain unknown. In this study, we investigated the expression, clinical significance, biological roles, and functional mechanism of PCNA-AS1 in NSCLC. Our results showed that PCNA-AS1 was upregulated in NSCLC tissues and cell lines, and correlated with TNM stages. Functional experiments showed that overexpression of PCNA-AS1 promoted NSCLC cell proliferation and cell cycle progression. Depletion of PCNA-AS1 inhibited NSCLC cell proliferation and cell cycle progression, and also inhibited NSCLC tumor growth
. Mechanistically, we found that PCNA-AS1 upregulated CCND1 expression. The expression of PCNA-AS1 was positively correlated with that of CCND1 in NSCLC tissues. Moreover, depletion of CCND1 abrogated the oncogenic roles of PCNA-AS1 in NSCLC. In conclusion, highly expressed PCNA-AS1 promotes NSCLC cell proliferation and oncogenic activity via upregulating CCND1. Our results imply that PCNA-AS1 might serve as a therapeutic target for NSCLC.
One of the most prevalent malignant primary brain tumors is primary glioma. Although glutathione peroxidase 8 (GPX8) is intimately associated with carcinogenesis, its function in primary gliomas has ...not yet been thoroughly understood. Here, we leveraged Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) database to investigate the association between GPX8 and overall survival (OS) of patients with primary gliomas, and our results showed that GPX8 expression was negatively correlated with OS. Moreover, the expression of GPX8 is significantly lower in normal tissue when compared to glioma tissue. According to results of univariate and multivariate analysis from CGGA using R studio, GPX8 is a valuable primary glioma prognostic indicator. Interestingly, high GPX8 expression is correlated positively with the hedgehog and kras signaling pathways and negatively with G2 checkpoint, apoptosis, reactive oxygen species (ROS) pathway, and interferon gamma pathway, which could be beneficial for the proliferation of glioma cells. Furthermore, GPX8 knockdown caused G1 cell cycle arrest, increased cell death, and reduced colony formation in U87MG and U118MG cells. In conclusion, GPX8 is a promising therapeutic target and meaningful prognostic biomarker of primary glioma.
Many molecular alterations are shared by embryonic liver development and hepatocellular carcinoma (HCC). Identifying the common molecular events would provide a novel prognostic biomarker and ...therapeutic target for HCC.
Expression levels and clinical relevancies of SLC38A4 and HMGCS2 were investigated by qRT-PCR, western blot, TCGA and GEO datasets. The biological roles of SLC38A4 were investigated by functional assays. The downstream signalling pathway of SLC38A4 was investigated by qRT-PCR, western blot, immunofluorescence, luciferase reporter assay, TCGA and GEO datasets.
SLC38A4 silencing was identified as an oncofetal molecular event. DNA hypermethylation contributed to the downregulations of Slc38a4/SLC38A4 in the foetal liver and HCC. Low expression of SLC38A4 was associated with poor prognosis of HCC patients. Functional assays demonstrated that SLC38A4 depletion promoted HCC cellular proliferation, stemness and migration, and inhibited HCC cellular apoptosis in vitro, and further repressed HCC tumorigenesis in vivo. HMGCS2 was identified as a critical downstream target of SLC38A4. SLC38A4 increased HMGCS2 expression via upregulating AXIN1 and repressing Wnt/β-catenin/MYC axis. Functional rescue assays showed that HMGCS2 overexpression reversed the oncogenic roles of SLC38A4 depletion in HCC.
SLC38A4 downregulation was identified as a novel oncofetal event, and SLC38A4 was identified as a novel tumour suppressor in HCC.
The cell cycle regulator cyclin D3 (CCND3) is highly expressed in multiple myeloma (MM) and it promotes MM cell proliferation. After a certain phase of cell cycle, CCND3 is rapidly degraded, which is ...essential for the strict control of MM cell cycle progress and proliferation. In the present study, we investigated the molecular mechanisms regulating CCND3 degradation in MM cells. By utilizing affinity purification-coupled tandem mass spectrometry, we identified the deubiquitinase USP10 interacting with CCND3 in human MM OPM2 and KMS11 cell lines. Furthermore, USP10 specifically prevented CCND3 from K48-linked polyubiquitination and proteasomal degradation, therefore enhancing its activity. We demonstrated that the N-terminal domain (aa. 1-205) of USP10 was dispensable for binding to and deubiquitinating CCND3. Although Thr283 was important for CCND3 activity, it was dispensable for CCND3 ubiquitination and stability modulated by USP10. By stabilizing CCND3, USP10 activated the CCND3/CDK4/6 signaling pathway, phosphorylated Rb, and upregulated CDK4, CDK6 and E2F-1 in OPM2 and KMS11 cells. Consistent with these findings, inhibition of USP10 by Spautin-1 resulted in accumulation of CCND3 with K48-linked polyubiquitination and degradation that synergized with Palbociclib, a CDK4/6 inhibitor, to induce MM cell apoptosis. In nude mice bearing myeloma xenografts with OPM2 and KMS11 cells, combined administration of Spautin-l and Palbociclib almost suppressed tumor growth within 30 days. This study thus identifies USP10 as the first deubiquitinase of CCND3 and also finds that targeting the USP10/CCND3/CDK4/6 axis may be a novel modality for the treatment of myeloma.
•The Tieshan complex body (TCB) is actually a potassic metamorphic complex.•The K-feldspar in TCB is mainly microcline, indicating its hydrothermal origin.•Hydrothermal quartz and melanite, combining ...K-feldspar, confirmed the origin of TCB.•Massive potassic metasomatism indicates huge potential of rare earth oxide resources.•The 39Ar-40Ar age of feldspars is 108 – 126 Ma, suggesting the Mesozoic alteration event.
Tieshan complex body (TCB) is located in Zhenghe County on the border of Zhejiang and Fujian, covering an area of about 5.7 km2. Tieshan complex body (TCB) is the most developed metasomatised area in the southeast of China, which was misunderstood as a syenite intrusion.
Much Study has carried on at Shizigang in the southwest of the TCB. The alkali metasomatites are composed of feldspar, pyroxene, amphibole, biotite and melanite et al. Potassic feldspars in Complex body have four kinds of forms and can be separated into three stages: (1) one in facial alkali alteration and one in alkali alteration with melanites, (2) one in light alkali feldspar veins, and (3) one in dark alkali feldspar veins and.
Pyroxenes had three kinds of forms: some in breccias, some in feldspar and some accompanied with amphiboles. Amphiboles had two kinds of forms: in breccias and scatter in feldspars in the veins, its mineral compositions are composed of basaltic hornblende, ferrous pargasite, actinolite and ferroactinolite, all belong to calcic amphibole subgroup. Biotites are scatteredin breccias and in the veins or which is the product of metasomatised pyroxenes. The compositions of biotites show low-Ti and Fe, but high-Mg, which were the thermal products of a higher oxygen fugacity. Melanites occurred as layers and belts, which were metasomatised by feldspars and epidotes and amphiboles and carbonates and sericites and diopsides, their ingredients are solid solution series between andradite and Grossular and reflect the melanites were formed in the relative oxidative, alkaline environment.
X-ray powder diffraction and infrared spectrum analyses of K-feldspar from early alkali feldspar provide degrees of ordering of 0.71–0.80, structural parameters of 1.27–1.61, triclinicities of 0.23–0.29, T1 (o) + T1 (m) of 0.86–0.90 degrees of ordering of 0.67–0.88 from late K-feldspar, its structural parametersof 1.10–1.91, triclinicities of 0.30–0.70, T1 (o) + T1(m) of 0.84–0.93. Both two kinds of alkali feldspars are microcline, most adularia. Their structure temperatures vary from 200 to 370 °C which are the highest temperatures at which K-feldspars were formed. Thus, it is concluded the K-feldspars in Tieshan is originated from thermal fluid, and the fluid was potassium-rich and a little rich in sodium at the later stage.
The 39Ar-40Ar age of feldspars shows 118.68 ± 7.70 Ma and 114.61 ± 6.74 Ma, which represent the ages of early stage facial alkali alteration and late stage dark alkali feldspar veins respectively. It is obvious that an original granites were formed at about 250 to 255 Ma, but all the rocks were considered to be strongly metasomatised by alkali fluid later, most occurred during 108–126 Ma in Yanshanism. Metasomatism of the TCBreflected that complex history of the region. The metasomatised rocks include fenite and amphibole feldsparite. Fenite, especially apatite-rich fenite is associated with REE mineralization, which is helpful to understand the mechanism of a large scale of rare earth deposits in the region.
The Yongping copper deposit is located in the Gandongbei metallogenic belt, South China. Stratiform-like copper ore bodies are hosted in limestones of the Upper Carboniferous Outangdi Formation. ...These ore bodies were previously believed to be products of the Carboniferous sedimentary exhalative (Sedex) mineralization, but they also appear to be related to the Late Mesozoic intermediate-acidic stocks at Yongping. The ore minerals are pyrite, chalcopyrite, with minor magnetite, sphalerite and galena. The gangue minerals are quartz, sericite, garnet, diopside, scapolite, wollastonite, tremolite, epidote, calcite and chlorite. Four stages of alteration and mineralization can be observed. Garnet, diopside and scapolite were formed in the earliest prograde skarn stage. The pre-ore barren quartz–pyrite veins that accompany tremolite, epidote, magnetite and chlorite, were subsequently formed due to the destruction of the earlier skarn. The stratiform-like copper ore bodies, with minor quartz–polymetallic veins, were formed in the main mineralization stage. The post-ore stage is characterized by late quartz–calcite±pyrite veins. Fluid inclusions in quartz from the pre-ore barren quartz–pyrite veins, stratiform-like copper ore bodies, and post-ore quartz–calcite±pyrite veins were studied. Fluid inclusion petrography shows that two-phase liquid-rich (type I), two-phase vapor-rich (type II), and halite-bearing (type III) fluid inclusions are present in these three generations of hydrothermal quartz. Type II and type III inclusions occur only in quartz from the stratiform-like copper ore bodies, whereas type I inclusions occur in all stages of hydrothermal quartz. Type I inclusions in pre-ore quartz–pyrite veins have homogenization temperatures of 300–398°C and salinities of 3.6–8.1wt.% NaCl equivalent. Type II and coexisting type III inclusions in the stratiform-like copper ore bodies share similar homogenization temperatures of 233–324°C and two contrasting salinity groupings of 0.4–3.2wt.% and 28.2–39.0wt.% NaCl equivalent, respectively. The coexistence of type II and type III inclusions and their similar homogenization temperatures but contrasting salinities suggest that fluid boiling processes occurred. Type I inclusions in the post-ore quartz–calcite veins have homogenization temperatures of 122–250°C and salinities of 0.2–6.8wt.% NaCl equivalent. The hydrogen and oxygen isotopic compositions of hydrothermal quartz indicate that the mineralizing fluids gradually evolved from a magmatic to meteoric source. The Pb–Pb dating of pyrite from stratiform-like copper ore bodies suggests that mineralization took place in the Jurassic. The skarn alteration, inferred boiling fluid inclusion assemblages, stable isotopic features of magmatic fluids, and Jurassic ages imply that the Yongping copper deposit is a Jurassic skarn copper deposit rather than a Carboniferous Sedex deposit.
•Intensive skarn alteration took place during the copper mineralization.•Ore-forming fluids are derived from magmatic waters.•Fluid boiling induced metal precipitation from hydrothermal solutions.•The Pb–Pb ages of pyrite from copper ore bodies are the Early Cretaceous.•It is an Early Cretaceous skarn deposit instead of a Carboniferous Sedex deposit.
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