Upregulation of LINC00659 expression predicts a poor prognosis and promotes migration and invasion of gastric cancer cells
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ABSTRACT:
SUBMITTER: Gong P
PROVIDER: S-EPMC8161466 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:G-protein-coupled receptors (GPCRs) are the most prominent family of cell surface receptors, which can regulate various biological functions and play an essential role in many diseases. GPR176 is a member of the GPCRs family and has been rarely studied in cancer. We aim to investigate the diagnostic and prognostic value of GPR176 in gastric cancer (GC) and explore its potential mechanism. Through the TCGA database and real-time quantitative PCR, we found that the expression level of GPR176 was significantly increased in GC and had good value in the diagnosis and prognosis of GC. Vitro experiments revealed that GPR176 could promote the proliferation, migration, and invasion of GC cells and may be involved in regulating multiple tumors and immune-related signaling pathways. In addition, we found that GPR176 is associated with GC immune infiltration and may affect the immune efficacy of GC patients. In summary, the high GPR176 expression level was associated with poor prognosis, more robust immune infiltration, and worse immunotherapy efficacy in GC patients, suggesting that GPR176 may be an immune-related biomarker for GC that can promote the proliferation, migration, and invasion of GC cells.
| S-EPMC10250322 | biostudies-literature
Project description:BackgroundsThe deubiquitinating enzyme OTUB1 participates in multiple cellular processes. However, its expression and functions in gastric adenocarcinoma remains unknown. The aim of this study was to investigate the expression of OTUB1 and its biological role in gastric adenocarcinoma.MethodsWe used immunohistochemistry to analyze OTUB1 expressions levels in 80 paired samples of gastric adenocarcinoma and adjacent normal tissue (ANT) and 30 samples of intraepithelial neoplasia (IN). We also analyzed the correlation between OTUB1 expression and clinicopathological parameters and patient survival status. Moreover, we performed wound-healing, transwell, RT-qPCR and Western blot assays to evaluate the impact of OTUB1 on tumor migration and invasion.ResultsIn gastric adenocarcinomas, staining for OTUB1 was localized in the cytoplasm. The proportion of samples that expressed OTUB1 and the intensity of its expression were much higher in gastric adenocarcinoma tissues (61 out of 80, 76.25%) than that in either IN (10 out of 30, 33.33%, p<0.001) or ANT (7 out of 80, 8.75%, p<0.001) samples. In malignant cases, higher expression OTUB1 levels were significantly associated with deeper tumor invasion depths (p=0.02), advanced lymph node status (p=0.008) and TNM stage (p=0.001), lymph duct invasion (p<0.001) and nerve invasion (p=0.013). Univariate and multivariate Cox regression analyses revealed that OTUB1 was an independent risk factor for disease-specific survival but not disease-free survival. In vitro wound-healing and transwell assays showed that OTUB1 overexpression promoted tumor cell migration and invasion in gastric cancer cells.ConclusionOTUB1 contributes to gastric cancer development by enhancing tumor invasiveness. Targeting OTUB1 should be considered in future molecular therapies.
| S-EPMC4891435 | biostudies-literature
Project description:Background: The aim of this study was to investigate the prognostic significance of faciogenital dysplasia 6 (FGD6) in gastric cancer (GC). Methods: The data of GC patients from The Cancer Genome Atlas (TCGA) database were used for the primary study. Then, our data were validated by the GEO database and RuiJin cohort. The relationship between the FGD6 level and various clinicopathological features was analyzed by logistic regression and univariate Cox regression. Multivariate Cox regression analysis was used to evaluate whether FGD6 was an independent prognostic factor for survival of patients with GC. The relationship between FGD6 and overall survival time was explored by the Kaplan-Meier method. In addition, gene set enrichment analysis (GSEA) was performed to investigate the possible biological processes of FGD6. Results: The FGD6 level was significantly overexpressed in GC tissues, compared with adjacent normal tissues. The high expression of FGD6 was related to a high histological grade, stage, and T classification and poor prognosis of GC. Multivariate Cox regression analysis showed that FGD6 was an independent prognostic factor for survival of patients with GC. GSEA identified that the high expression of FGD6 was mainly enriched in regulation of actin cytoskeleton. Conclusion: FGD6 may be a prognostic biomarker for predicting the outcome of patients with GC.
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Project description:BackgroundRecent evidence has shown that Solute Carrier Family 39 Member 10 (SLC39A10) promoted tumor progression in several cancer types. The study intended to explore the expression and function of SLC39A10 in hepatocellular carcinoma (HCC).MethodsMultiple bioinformatics analyses were used to evaluate SLC39A10 expression and potential role in HCC. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to confirm SLC39A10 expression. Intro studies were performed to assess the effects of SLC39A10 on HCC cells proliferation and migration. Furthermore, flow cytometry was conducted to identify its specific function in apoptosis of HCC.ResultsSLC39A10 was significantly over-expressed in HCC samples from both bioinformatic databases and our cohort. Survival analyses suggested patients with high expression of SLC39A10 had poor overall survival and disease-free survival (P-value <0.01). Further, the expression of SLC39A10 was positively correlated with tumor-infiltrating lymphocytes and some immune checkpoints like CTLA4, TIM3 and TGFB1. In HCC cell lines, SLC39A10 knockdown inhibited cells proliferation and migration, but promoted apoptosis.ConclusionAn increased SLC39A10 expression was found and served as an unfavorable indicator of survival in HCC. Further studies suggested SLC39A10 promotes tumor aggressiveness and may provide a novel target for HCC therapy.
| S-EPMC8357404 | biostudies-literature
Project description:Latent transforming growth factor-β-binding protein (LTBP)2 is a member of the fibrillin/LTBP superfamily of extracellular matrix proteins, and has been demonstrated to exhibit tumor-promoting and tumor-suppressive functions in different types of cancer. However, the function of LTBP2 in gastric cancer (GC) remains unknown. The aim of the present study was to investigate the expression and molecular function of LTBP2 in GC, and to evaluate its prognostic value for patients with GC. The results revealed that the expression of LTBP2 was upregulated in GC tissues and cell lines. Increased LTBP2 expression was associated with poor overall survival in patients with early-stage [tumor-node-metastasis (TNM) I/II] and late-stage (TNM III/IV) GC. Furthermore, silencing of LTBP2 effectively suppressed the proliferation, migration, invasion and epithelial-mesenchymal transition in GC cells. These results suggested that LTBP2 may be considered as a potential therapeutic target and a promising prognostic biomarker for human GC.
| S-EPMC5919710 | biostudies-literature
Project description:PurposeThe epithelial-mesenchymal transition (EMT) is a key hallmark of cancer which promotes malignant progression, especially during the process of cancer invasion. A better understanding of EMT will help elucidate the molecular mechanism underlying colorectal cancer (CRC) metastasis and may provide new insights into the identification of potential biomarkers and therapeutic targets.MethodsA series of bioinformatic approaches were combined and identify GLI3 as a potential key regulator in EMT. In vitro experiments were performed to knockdown GLI3 expression in two CRC cell lines and to reveal the oncogenic role of GLI3 in CRC. qRT-PCR and western blot were performed to show the influence of GLI3 in EMT and downstream pathways. The Kaplan-Meier analysis and log-rank test were used to evaluate the prognostic value of GLI3 in CRC patients.ResultsGLI3 was identified as a key regulator in coexpression and protein-protein interaction (PPI) networks involved in EMT. Bioinformatic analyses indicated that GLI3 had a high correlation with EMT markers in CRC. In vitro experiments showed that GLI3 knockdown attenuated the migratory and invasive capacities of CRC cells via influencing EMT property, especially by regulating phosphorylation of ERK signaling pathway. In addition, higher expression of GLI3 predicts worse prognosis in CRC patients.ConclusionsIn summary, we presented the first evidence that GLI3 could promote the migratory and invasive capacities of CRC cells by regulating the EMT process. Our study might provide some useful clues to a better understanding of GLI3 in EMT during CRC progression.
| S-EPMC7814942 | biostudies-literature
Project description:Previous cDNA microarray experiments revealed that the ATP-dependent DNA helicase Q4 (RECQL4) gene is overexpressed in hepatocellular carcinoma (HCC) tissues. However, the exact role of RECQL4 in HCC remains unknown. The present study aimed to investigate RECQL4 expression in HCC and to analyze the potential clinical implications of RECQL4 expression in HCC patients. The expression of RECQL4 mRNA was assessed in 205 samples of HCC tissues by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that the expression of RECQL4 mRNA in HCC tissues was significantly higher compared with adjacent normal liver tissues (P<0.001). The level of RECQL4 mRNA expression was associated with high a-fetoprotein (AFP) levels (>100 ng/ml), tumor size (>6 cm), and Barcelona Clinic Liver Cancer stage (all P<0.05). Kaplan-Meier survival analysis indicated that HCC patients with higher levels of RECQL4 expression exhibited significantly shorter disease-free survival (DFS) and overall survival (OS) times compared with those with low levels of expression. Multivariate survival analysis revealed that high RECQL4 expression was a significant independent predictor for DFS [HR, 1.635; 95% confidence interval (CI), 1.062-2.515; P=0.025] and OS (HR, 1.618; 95% CI, 1.050-2.493; P=0.029) of HCC patients. These data indicated that RECQL4 might be a novel diagnostic and prognostic biomarker for HCC patients.
| S-EPMC5835851 | biostudies-literature
Project description:Activin A is a member of the transforming growth factor‑β superfamily of cytokines and displays various pathophysiological activities, including regulation of muscle catabolism and atrophy. Activin A expression is upregulated in several human cancer types and in certain pathologies, its expression is associated with poor prognosis. In the present study, activin A expression was assessed in colorectal cancer (CRC) tissue specimens from 157 patients with primary CRC and the relationship between activin A levels and clinicopathological characteristics, including skeletal muscle mass, and prognosis, was determined. Furthermore, the effects of knockdown of endogenous or exposure to exogenous activin A on the malignant behavior of human CRC cell lines were investigated in vitro. The results indicated that activin A mRNA was significantly upregulated in CRC tumor tissues compared with normal intestinal epithelium. High activin A expression was significantly associated with shorter cancer‑specific survival (P=0.047) and overall survival (P=0.014). According to a multivariate analysis, tumor activin A levels were an independent prognostic factor for overall survival (P=0.001). However, activin A mRNA levels were not associated with the skeletal muscle index. The in vitro experiments demonstrated that exposure to exogenous activin A increased the proliferation, invasion and migration of CRC cell lines, whereas knockdown of endogenous activin A had the opposite effects. In conclusion, activin A is an autocrine and paracrine regulator of CRC cell proliferation and high tumor expression of activin A is associated with poor prognosis in patients with CRC.
| S-EPMC9073419 | biostudies-literature
Project description:Gastric cancer (GC) is a frequently occurring malignancy with high mortality rates. However, the underlying mechanism of GC progression is not very clear. The aim of this study is to reveal the inherent molecular mechanism and develop potential therapeutic targets for advanced GC. The microfibril-associated glycoprotein 1 (MAGP1), identified as a potential oncogene, was found upregulated in GC tissues and high MAGP1 expression was associated with aggressive clinicopathological features. Furthermore, the multivariate Cox regression analysis showed that high MAGP1 expression was an independent predictor of poor prognosis (HR = 2.37, 1.07-5.24; P = 0.033). Mechanistically, MAGP1 promoted the migration and invasiveness of GC cells. In addition, the genes co-expressed with MAGP1 were primarily enriched in focal adhesion and PI3K-Akt pathways. MAGP1 overexpression enhanced the phosphorylation of FAK, AKT, and mTOR, whereas its knockdown also inactivated these factors. Furthermore, the AKT inhibitor suppressed the phosphorylation of AKT, FAK, and mTOR in recMAGP1-treated AGS cells, as well as their migration and invasion capacities. Finally, correlation analysis indicated that MAGP1 is involved in AKT signaling in GC, and is clinically relevant. Taken together, MAGP1 is a promising prognostic marker and potential therapeutic target for advanced GC.
| S-EPMC6978879 | biostudies-literature
Project description:BackgroundThe deubiquitinase OTUB1 plays critical oncogenic roles and facilitates tumor progression in cancer. However, less is known regarding the aberrant expression, clinical significance and biological functions of the non-coding RNA OTUB1-isoform 2. We aimed to evaluate the OTUB1-isoform 2 levels in gastric cancer and their possible correlation with clinicopathologic features and patient survival to reveal its biological effects in gastric cancer progression.MethodsTotal RNA extraction was performed on 156 gastric cancer case samples, and RT-qPCR was conducted. Chi-square test analysis was used to calculate the correlation between pathological parameters and the OTUB1-isoform 2 mRNA levels. Kaplan-Meier and Cox proportional hazards analyses were used to analyze the overall survival (OS) and disease-free survival (DFS) rates. Nuclear and cytoplasmic RNAs were isolated to detect the subcellular localization of OTUB1-isoform 2. We also assessed whether overexpression of OTUB1-isoform 2 influenced in vitro cell proliferation, cell cycle progression, tumor cell invasion and migration, as well as in vivo nude mouse xenograft and metastasis models.ResultsThe OTUB1-isoform 2 expression levels were higher in the gastric cancer samples than in the paratumorous gland samples. OTUB1-isoform 2 expression levels tightly correlated with tumor size, lymph node metastasis and TNM staging. Higher OTUB1-isoform 2 expression levels led to significantly poorer OS and DFS rates, and a multivariate analysis revealed that OTUB1-isoform 2 was an independent risk factor for DFS. OTUB1-isoform 2 was predominantly localized in the cell nucleus. Ectopic overexpression of OTUB1-isoform 2 in gastric cancer cells stimulated proliferation by inducing G1-S transition, suppression of cell apoptosis and promotion of tumor cell invasion and migration. Finally, OTUB1-isoform 2 overexpression promoted tumor growth and tumor metastasis in nude mice models.ConclusionsOur study suggests that OTUB1-isoform 2 independently predicts poor prognosis and promotes tumor progression in gastric cancer. The non-coding RNA OTUB1-isoform 2 should be targeted in future molecular therapies.
| S-EPMC4807415 | biostudies-literature