Calcium-dependent activator protein for secretion 1 (CAPS1) has been reported to promote metastasis in colorectal cancer (CRC), however, the underlying mechanisms have not yet been elucidated. The present study revealed that exosomes derived from CAPS1-overexpressing CRC cells could enhance the migration of normal colonic epithelial FHC cells. GW4869, an inhibitor of exosomes, could attenuate the migration of FHC cells. Furthermore, liquid chromatography-mass spectrometry (LC-MS) and bioinformatics analysis demonstrated that overexpression of CAPS1 could alter the expression pattern of exosomal proteins involved in cell migration. Bone morphogenetic protein 4, which may serve vital roles in the process of CAPS1-induced cell migration, was downregulated in the exosomes. In summary, the present results demonstrated that CAPS1 promotes cell migration by regulating exosomes. Inhibiting the secretion of exosomes may be helpful for the treatment of patients with metastatic CRC.
H2A family member Z (H2AFZ) is a highly conserved gene encoding H2A.Z.1, an isoform of histone variant H2A.Z, and is implicated in cancer. In this study, we report that overexpression of H2AFZ is associated with tumor malignancy and poor prognosis in HCC patients. Functional network analysis suggested that H2AFZ mainly regulates cell cycle signaling and DNA replication via pathways involving several cancer-related kinases and transcription factor E2F1. Further studies revealed that H2AFZ overexpression is regulated by TP53 mutation and led to an attenuation of rapid proliferation phenotype and aggressive behavior in HCC cells. Moreover, we found that H2AFZ was related to immune infiltrations and was co-expressed with immune checkpoint genes, including CD274 (PD-L1), CTLA-4, HAVCR2 (TIM3), LAG3, PDCD1 (PD-1), and TIGIT (VSIG9) in HCC, indicating that H2AFZ-overexpressed HCC patients may be sensitive to immune checkpoint blockades (ICBs). Integrated analysis suggested that H2AFZhigh/TP53mut patients had the shortest OS and PFS time, but most likely to respond to ICBs. These findings indicate that the H2AFZ possesses potential value as a novel prognostic indicator for HCC patients and is correlated with immune infiltration in HCC, laying a foundation for future study of HCC investigation and intervention.
Metastasis of breast cancer represents the major reason for its poor prognosis, leading to high mortality. In breast cancer, a tumor suppressor gene TP53 is commonly mutated. TP53 mutation leads to an altered expression of various genes, an event that is associated with aggressive tumor and is a strong independent marker for survival. In this study, we identified a novel p53 target gene, immunoglobulin superfamily 9 (IGSF9). IGSF9 is generally down-regulated in breast cancer tissues. Loss of IGSF9 is associated with frequent metastasis and poor prognosis of breast cancer patients. Wild-type p53, but not R175H mutant, trans-activates the transcription of IGSF9 via binding to its promoter (−137 to −131 bp), inhibits epithelial-mesenchymal transition (EMT), consequently the inhibition of breast cancer cells migration and invasion. IGSF9 interacts with focal adhesion kinase (FAK) and inhibits FAK/AKT signaling activity. PND1186, FAK inhibitor, inhibits breast cancer metastasis induced by IGSF9 knockdown in vitro and in vivo. Taken together, IGSF9 is trans-activated by p53 and inhibits breast cancer metastasis by modulating FAK/AKT signaling pathway. IGSF9 could serve as a prognostic marker and potential therapeutic target for breast cancer.
ObjectiveTo evaluate the efficacy of different acupuncture therapies for radiotherapy-induced adverse effects (RIAEs) and find out the optimal scheme.MethodsEligible randomized controlled trials (RCTs) were collected from inception to June 2020 from 9 bibliographic databases. The risk of bias evaluation of the analyzed literature was carried out using the Cochrane risk-of-bias tool. Network meta-analysis was mainly performed using STATA 14.2 and OpenBUGS 3.2.3 by figuring out the network diagrams, league figures, and SUCRA values.ResultsA total of 41 studies with 3,011 participants reported data suitable for network meta-analysis. There was a low to moderate risk of bias in twenty of the articles. ST36 was the most widely prescribed acupoint. Based on network meta-analysis, four outcome indicators were described, namely, acupuncture + medication ranked first in treating radiation enteritis, moxibustion + medication ranked first in preventing radiotherapy-induced leukopenia, acupuncture + medication ranked first in preventing radioactive oral mucositis, and acupuncture ranked first in improving the stimulated salivary flow rate of radioactive xerostomia.ConclusionThe findings of the network meta-analysis manifested that acupuncture therapy combined with medication has superiority in most RIAEs, both reducing incidence and relieving symptoms. However, high-quality studies are still needed to provide conclusive evidence.Systematic review registrationhttps://inplasy.com/inplasy-2020-7-0054/, identifier: INPLASY202070054.
Background: Radiotherapy is the cornerstone in cancer treatment, and its adverse effects have been recognized widely nowadays. In response, effective and nontoxic therapies are in demand for patients affected by radiotherapy-induced adverse effects (RIAE). As a multitude of clinical studies have suggested that acupuncture therapies seem to be potential in treating RIAE, this study aims to make a systematic review and Bayesian network meta-analysis (NMA) to evaluate effectiveness and safety of different acupuncture treatments.
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