Beierbowden9700
Several ongoing phase I and II clinical trials are evaluating TLR9 agonists in combination with a variety of agents including chemotherapy, radiotherapy, targeted therapy, and immunotherapy agents. In this review article, we describe the distribution, structure and signaling of TLR9; discuss the results of preclinical studies of TLR9 agonists; and review ongoing clinical trials of TLR9 agonists singly and in combination in patients with advanced solid tumors.
The significance of periodic tryptophan protein 1 (PWP1) expression in human cancer and its molecular mechanism of action have not been reported so far.
Immunohistochemistry was performed to analyze the expression of PWP1 in non-small cell lung cancer (NSCLC) tissues and statistical analysis was applied to analyze the relationship between PWP1 expression and the clinicopathological factors. The effects of PWP1 on NSCLC proliferation and invasion were determined by colony formation, transwell and MTT assays. Western blot analysis (WB), dual-luciferase reporter gene assays and immunofluorescence staining were performed to demonstrate whether PWP1 stimulates Wnt pathway and inhibits Hippo pathway. Co-immunoprecipitation (Co-ip) assays were used to confirm the potential role of PWP1 in Wnt and Hippo signaling pathways.
PWP1 expression in NSCLC was higher than that in normal bronchial epithelium and normal submucosal glands. In addition, PWP1 expression had a positive correlation with poor differentiation, hnosis. PWP1 enhanced the activity of the Wnt pathway by interacting with DVL2, whereas PWP1 inhibited the activity of the Hippo pathway by interacting with Merlin. Together, these two effects promoted the detrimental biological behaviors of NSCLC cells.
Oral leukoplakia is the most common oral mucosal disease. A proportion of such cases can progress to oral squamous cell carcinoma (OSCC). The mechanism of oral leukoplakia malignant transformation is still unclear. In this study, we analyzed the expression of parathyroid hormone-like hormone (
) in oral leukoplakia and the effect on prognosis, so as to find reliable molecular markers that can predict oral leukoplakia malignant transformation.
We measured PTHrP which is coded by
in oral leukoplakia tissues of 79 cases (30 cases progressed to OSCC and 49 did not) and analyzed the clinical outcomes. Then,
expression was reduced using lentivirus-mediated small hairpin RNA (shRNA) interference to determine the biological role of
in DOK cells.
PTHrP was found to be highly expressed in 38% of tissues of oral leukoplakia. There was weak or no PTHrP expression in 25 patients, moderate expression in 24 patients, and strong in 30 patients with oral leukoplakia. The expression level was associated with the degree of atypical hyperplasia and poor prognosis. The cell proliferation, invasion, migration, cell cloning, and cell cycle were affected after reducing
expression.
Our data suggest that either
or PTHrP plays a key role in the malignant transformation of oral leukoplakia and might be a reliable biomarker for predicting the carcinogenesis of oral leukoplakia.
Our data suggest that either PTHLH or PTHrP plays a key role in the malignant transformation of oral leukoplakia and might be a reliable biomarker for predicting the carcinogenesis of oral leukoplakia.
DNA methylation plays an important role in regulating gene expression. Methyl-CpG-binding domain (MBD) proteins recognize and bind to methylated DNA, which mediate gene silencing by the interaction with deacetylases and histone methyltransferases. MBD2 has been reported in various human cancers; however, its clinical implication and potential regulatory role in renal cell carcinoma (RCC) have not been elaborated.
In the study, we estimated the expression and prognostic value of
in RCC cell lines and tissues by Western blotting and immunohistochemistry. The associations of
expression and pathological characters and survival in RCC patients were performed using χ2 and Kaplan-Meier survival analysis, respectively. Univariate and multivariable Cox regression analyses suggested the independent predictors in RCC prognosis. The functional role of
in RCC progression was assessed by in vitro cell experiments. In addition, we identified the
-mediated alterations of protein-related proliferation and EMT markers in RCC cells after
overexpression and knockdown.
We found that the protein levels of
were upregulated in RCC cells and tissues. High
expression was related to TNM stage and predicted poorer survival in RCC. Enforced expression of
significantly promoted the proliferation, cycle progress, invasion and migration of RCC cells in vitro. However, downregulating
remarkably weakened the above cell functions. Mechanistically, the promotive effect of
overexpression may be regulated by its effects on
and
expression and EMT process.
These results indicated that
confers an oncogenic function in the malignant progression of RCC.
could be served as a meaningful prognostic biomarker and a latent therapeutic target in RCC patients.
These results indicated that MBD2confers an oncogenic function in the malignant progression of RCC. MBD2 could be served as a meaningful prognostic biomarker and a latent therapeutic target in RCC patients.
Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers and is ranked as the fifth most common malignancy. Androgen receptor (AR) may promote the progression of HCC at an early stage of the disease. However, this study identified miR-135b-5p as an AR upstream regulator can suppress AR protein expression and inhibit HCC proliferation, consistent with the idea that AR expression is negatively correlated with HCC progression.
The target microRNAs were predicted using online databases (TargetScan, miRDB, and MicroCosm Targets). Cell proliferation ability was measured by MTT and colony formation assay. check details Western blot was performed to analyze the expression levels of AR, HIF-2α, c-Myc, and p27, which are related to HCC proliferation. Chromatin immunoprecipitation (ChIP) assay and luciferase reporter assay were carried out to investigate the mechanism by which miR-135b-5p decreases AR expression.
miR-135b-5p suppresses HCC cell proliferation and AR expression. Downregulation of AR expression by miR-135b-5p may in turn transcriptionally modulate HIF-2α expression via direct binding of AR to the androgen response element (ARE) in the HIF-2α promoter. Further dissection of the mechanism revealed that AR-modulated HIF-2α could suppress c-Myc expression resulting in increased p27 expression that likely contributes to the suppression of proliferation in HCC cells.
miR-135b-5p suppresses HCC cell proliferation via targeting AR-modulated HIF-2α/c-Myc/p27 signals, which may help to develop more effective therapies to prevent HCC progression.
miR-135b-5p suppresses HCC cell proliferation via targeting AR-modulated HIF-2α/c-Myc/p27 signals, which may help to develop more effective therapies to prevent HCC progression.
Tongue squamous cell carcinoma (TSCC) accounts for one-third of oral cancers. Previous studies had reported that lncRNA/miRNA regulated the biological behaviors of different cancer cells. However, the mechanisms of PART1 in regulating tumorigenesis and TSCC development via targeting miR-503-5p had not been studied.
The expressions of PART1 and miR-503-5p in tissues and cultured cell lines were detected by qRT-PCR. StarBase 3.0 was used to predict the binding sites of PART1, then dual-luciferase assay and RNA pull-down assay were executed to confirm whether miR-503-5p was a target of PART1. TSCC cells were co-transfected with PART1-overexpressed plasmid or miR-503-5p mimics in vitro, and the transfection efficiency was evaluated through qRT-PCR. Western blot was performed to assess the expressions of EMT-related proteins. CCK-8 and clone formation assays were conducted to detect cell proliferation, TUNEL assay was used to detect apoptosis, and transwell assay was executed to test migration and invasion.
The low PART1 expression and high miR-503-5p expression were found in TSCC tissues and cell lines (CAL-27 and SCC9). PART1 expression was positively correlated with patients' prognosis. The targeting and binding relationship between PART1 and miR-503-5p was confirmed, and overexpressed PART1 diminished the expression of miR-503-5p as well. Moreover, PART1 facilitated apoptosis, inhibited proliferation, invasion and migration of TSCC cells, and these influences were impeded by miR-503-5p overexpression.
LncRNA PART1 played a cancer-suppressing role in TSCC by targeting miR-503-5p, which provided a potential target for TSCC treatment.
LncRNA PART1 played a cancer-suppressing role in TSCC by targeting miR-503-5p, which provided a potential target for TSCC treatment.
The chemoresistance and toxicity of traditional chemotherapeutic drugs have become obstacles to their antitumor effects in ovarian cancers. Therefore, it is particularly important to develop new anticancer drugs to increase target sensitivity and reduce the toxicity of chemotherapy drugs. As key organelles, the endoplasmic reticulum and mitochondria play important role in chemoresistance. Cells become resistant to drugs by maintaining the homeostasis of the endoplasmic reticulum and mitochondria. Chaetomugilin J, a metabolite isolated from
, belongs to the Chaetomium family and exhibits potent cytotoxicity. In this study, we aimed to explore the mechanistic link between apoptosis and endoplasmic reticulum stress, mitophagy and mitochondrial dysfunction induced by chaetomugilin J combined with cisplatin in the ovarian cancer cell line A2780.
Chaetomugilin J was identified by chemical methods. Cell viability was measured by an MTT assay. The apoptosis, mitochondrial membrane potential, and intracellular rtin inhibited pink1/parkin mediated mitophagy increased mitochondrial dysfunction in the A2780 cells and enhanced apoptosis induced by cisplatin in the ovarian cancer cell line A2780. But this process was not related to endoplasmic reticulum apoptotic pathway.
Glioma is the most aggressive human brain tumor. Recent studies revealed that microRNAs play vital roles in glioma. However, the function of microRNA-525-5p (miR-525-5p) in glioma remains unclear.
qRT-PCR and Western blotting were used to evaluate mRNA and protein levels in glioma tissues and cells. Colony formation, CCK-8, and Edu assays evaluated the growth of glioma cells. Wound-healing, transwell, and 3D invasion assays examined the migration and invasion activities of glioma cells. Luciferase reporter assays assessed the regulatory relationship interaction between miR-525-5p and Stat-1. A mouse xenograft model was used to examine the effect of miR-525-5p on glioma in vivo.
miR-525-5p expression was downregulated in glioma tissues and cells. Overexpressing miR-525-5p decreased the growth of glioma cells and reduced the migration, invasion, and epithelial-mesenchymal transition of glioma cells. Bioinformatics analysis identified Stat-1 as a potential target of miR-525-5p, and dual luciferase reporter assays revealed that miR-525-5p negatively regulates Stat-1. Decreased Stat-1 led to the inhibition of FOXM1, affecting NF-κB signaling activity. Overexpressing miR-525-5p reduced tumor development in vivo.
miR-525-5p negatively regulates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in glioma, and Stat 1 is a target of miR-525-5p. miR-525-5p may be a potential target for glioma treatment.
miR-525-5p negatively regulates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in glioma, and Stat 1 is a target of miR-525-5p. miR-525-5p may be a potential target for glioma treatment.
