Decreased expression of the long non-coding RNA SLC7A11-AS1 predicts poor prognosis and promotes tumor growth in gastric cancer.
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ABSTRACT:
SUBMITTER: Luo Y
PROVIDER: S-EPMC5762530 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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| S-EPMC5493660 | biostudies-literature
Project description:Colon cancer is the main cause of cancer mortality worldwide. Its poor prognosis is mainly ascribed to high recurrence rates. Identifying novel prognostic biomarkers and therapeutic key points for management is crucial and important. Long non-coding RNAs (lncRNAs) are a class of RNAs, which have various roles in carcinogenicity and molecular mechanisms. The lncRNA small nucleolar RNA host gene 1 (SNHG1) contributes to the promotion of tumor development, however, the connections between SNHG1 and colon cancer are still unclear. The aim of the present study was to investigate the clinical significance, the biological functions, and the potential mechanism of SNHG1 in colon cancer. In the present study, we referred to the Oncomine database and used RT-qPCR to determine that SNHG1 expression was significantly higher both in colon cancer tissues and cancerous cell lines than in normal samples. Cell functional experiments were performed after knockdown of SNHG1, including Cell Counting Kit-8 assay, colony formation assay, Transwell® assay, and flow cytometric analyses of cell apoptosis, which suggested that SNHG1 stimulated colon cancer cell proliferation, promoted cell invasion and migration, and inhibited apoptosis. Immunohistochemical staining and western blotting experiments revealed that in colon cancer cells with SNHG1 knockdown, β-catenin, c-Myc and cyclin D1 protein levels were decreased, while E-cadherin was increased, which suggested that SNHG1 promoted colon cancer cell proliferation, migration and invasion through the Wnt/β-catenin signaling pathway. Our results indicated that SNHG1 and its interrelated components may be future therapeutic targets of carcinoma of the colon.
| S-EPMC6059747 | biostudies-literature
Project description:LINC00092 and MCM3AP-AS1 long non-coding RNAs (LncRNAs) play significant roles in the development and pathogenesis of many cancers. However, their expression levels and prognostic values were not evaluated in human gastric adenocarcinoma (GAC). Therefore, the present study aimed to investigate the clinico-pathological correlations of LINC00092 and MCM3AP-AS1, LncRNAs expression in GAC, and evaluate their prognostic values. The expression of LINC00092 and MCM3AP-AS1 was detected in 89 GAC tissues by quantitative real-time reverse-transcription PCR (qRT-PCR). Our results showed that LINC00092 and MCM3AP-AS1 are overexpressed in GAC patients and positively correlated with GAC invasion and vascular, peritoneal, and lymph node metastasis (P < 0.05). Furthermore, the results indicated that MCM3AP-AS1 (P = 0.0225) and LINC00092 (P < 0.001) have positive correlations with GAC patients' overall survival. Altogether, the present results indicated that LINC00092 and MCM3AP-AS1 overexpression is associated with clinico-pathological characteristic of GAC patients. In addition, both of these LncRNAs may have prognostic value for estimation of patients' overall survival.
| S-EPMC11373733 | biostudies-literature
Project description:Background:Lung cancer (LC) is one of the leading causes of cancer-related mortality in China and worldwide. Despite the progress in diagnosis and treatment of LC, the prognosis of LC remains poor. Studies have demonstrated that long non-coding RNAs (lncRNAs) play a critical role in carcinogenesis and cancer development. Methods:Here we examined the expression and potential function of lnc-RAB11B-AS1 in LC both in vitro and in vivo. All experiments in this study were conducted using A549 and PC-9 cell lines according to protocols described in this paper. The clinic characteristics were analyzed using logistic regression, cox model, log rank test, biochemical analysis using qRT-PCR, transfections, nude mice model, and cell biological analysis using Transwell assay, CCK-8 assay, flow cytometry, and rescue experiments, and immunohistochemistry. Results:The results showed that lnc-RAB11B-AS1 was significantly overexpressed in LC tissues compared to the corresponding non-tumor tissues. Patients with a higher level of lnc-RAB11B-AS1 expression showed a poorer overall survival rate. Functionally, overexpression of lnc-RAB11B-AS1 promotes cell proliferation, migration and invasion abilities of LC cell lines, which suggests lnc-RAB11B-AS1 may play an oncogenic role in LC. lnc-RAB11B-AS1 was located in physical contiguity with RAB11B gene and found positively regulates the RAB11B expression, and the protein levels of RAB11B in LC tissues also found to positively correlated with the level of lnc-RAB11B-AS1 expression. RAB11B silencing partially abrogated lnc-RAB11B-AS1-induced proliferation of the LC cell lines used in this study. Conclusions:This study provided a novel evidence into the function of lncRNA-driven carcinogenesis. Our findings highlighted the importance of lnc-RAB11B-AS1 and RAB11B in LC progression and indicated that lnc-RAB11B-AS1 may serve as a novel and valuable prognostic biomarker for LC.
| S-EPMC7290536 | biostudies-literature
Project description:Emerging evidence suggests that long non‑coding RNAs (lncRNAs) play pivotal roles in cancer progression, including in intrahepatic cholangiocarcinoma (IHCC). The overexpression of lncRNA ZEB1 antisense 1 (ZEB1‑AS1) has been discovered in several types of cancer; however, the clinical significance and functional role of ZEB1‑AS1 in IHCC have not yet been determined. In the present study, ZEB1‑AS1 was found to be upregulated in IHCC cell lines and tissues. A high ZEB1‑AS1 expression was associated with clinical progression and a poor survival of patients with IHCC, and was identified as an independent risk factor for a poor prognosis. In addition, ZEB1‑AS1 promoted the proliferation and metastasis of IHCC cells both in vitro and in vivo. ZEB1‑AS1 was demonstrated to increase the expression of ZEB1 by sponging miR‑200a and to thereby accelerate epithelial‑mesenchymal transition (EMT). On the whole, the findings of the present study demonstrate that ZEB1‑AS1 promotes proliferation and metastasis in IHCC, and induces EMT through the miR‑200a/ZEB1 signaling pathway. ZEB1‑AS1 may thus be a promising prognostic biomarker and essential therapeutic target for IHCC.
| S-EPMC7170034 | biostudies-literature
Project description:BackgroundGastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. Minichromsome maintenance proteins family member 8 (MCM8) assists DNA repair and DNA replication. MCM8 exerts tumor promotor function in multiple digestive system tumors. MCM8 is also considered as a potential cancer therapeutic target.MethodsBioinformatics methods were used to analyze MCM8 expression and clinicopathological significance. MCM8 expression was detected by immunohistochemistry (IHC) staining and qRT-PCR. MCM8 functions in GC cell were explored by Celigo cell counting, colony formation, wound-healing, transwell, and annexin V-APC staining assays. The target of MCM8 was determined by human gene expression profile microarray. Human phospho-kinase array kit evaluated changes in key proteins after ribosomal protein S15A (RPS15A) knockdown. MCM8 functions were reassessed in xenograft mouse model. IHC detected related proteins expression in mouse tumor sections.ResultsMCM8 was significantly upregulated and predicted poor prognosis in GC. High expression of MCM8 was positively correlated with lymph node positive (p < 0.001), grade (p < 0.05), AJCC Stage (p < 0.001), pathologic T (p < 0.01), and pathologic N (p < 0.001). MCM8 knockdown inhibited proliferation, migration, and invasion while promoting apoptosis. RPS15A expression decreased significantly after MCM8 knockdown. It was also the only candidate target, which ranked among the top 10 downregulated differentially expressed genes (DEGs) in sh-MCM8 group. RPS15A was identified as the target of MCM8 in GC. MCM8/RPS15A promoted phosphorylation of P38α, LYN, and p70S6K. Moreover, MCM8 knockdown inhibited tumor growth, RPS15A expression, and phosphorylation of P38α, LYN, and p70S6K in vivo.ConclusionsMCM8 is an oncogene and predicts poor prognosis in GC. MCM8/RPS15A facilitates GC progression.
| S-EPMC11236911 | biostudies-literature
Project description:BackgroundGastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Long noncoding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. Although downregulation of lncRNA GAS5 (Growth Arrest-Specific Transcript) in several cancers has been studied, its role in gastric cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of GAS5 in gastric cancer.MethodsExpression of GAS5 was analyzed in 89 gastric cancer tissues and five gastric cancer cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of GAS5. The effect of GAS5 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by hochest stainning. Gastric cancer cells transfected with pCDNA3.1 -GAS5 were injected into nude mice to study the effect of GAS5 on tumorigenesis in vivo. Protein levels of GAS5 targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed).ResultsWe found that GAS5 expression was markedly downregulated in gastric cancer tissues, and associated with larger tumor size and advanced pathologic stage. Patients with low GAS5 expression level had poorer disease-free survival (DFS; P = 0.001) and overall survival (OS; P < 0.001) than those with high GAS5 expression. Further multivariable Cox regression analysis suggested that decreased GAS5 was an independent prognostic indicator for this disease (P = 0.006, HR = 0.412; 95%CI = 2.218-0.766). Moreover, ectopic expression of GAS5 was demonstrated to decrease gastric cancer cell proliferation and induce apoptosis in vitro and in vivo, while downregulation of endogenous GAS5 could promote cell proliferation. Finally, we found that GAS5 could influence gastric cancer cells proliferation, partly via regulating E2F1 and P21 expression.ConclusionOur study presents that GAS5 is significantly downregulated in gastric cancer tissues and may represent a new marker of poor prognosis and a potential therapeutic target for gastric cancer intervention.
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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.
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Project description:Liver kinase B1 (LKB1) has been identified as a critical modulator involved in cell proliferation and polarity. The purpose of the current study was to characterize the expression pattern of LKB1 and assess the clinical significance of LKB1 expression in pancreatic ductal adenocarcinoma (PDAC) patients. LKB1 mRNA expression which was analyzed in 32 PDAC lesions and matched non-tumor tissues, was downregulated in 50% (16/32) of PDAC lesions. Similar results were also obtained by analyzing three independent datasets from Oncomine. Protein expression of LKB1 was significantly reduced in 6 PDAC cell lines and downregulated in 31.3% (10/32) of PDAC lesions compared to matched non-tumorous tissues, as determined by Western blot analysis. Additionally, tissue microarray containing 205 PDAC specimens was evaluated for LKB1 expression by IHC and demonstrated that reduced expression of LKB1 in 17.6% (36/205) of PDAC tissues was significantly correlated with clinical stage, T classification, N classification, liver metastasis and vascular invasion. Importantly, Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of PDAC and found that LKB1 protein expression was one of the independent prognostic factors for overall survival of PDAC patients.
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Project description:BackgroundStriatin-interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth. But the role of STRIP2 in lung adenocarcinoma (LUAD) has not been discovered clearly. Thus, the aim of our study is to explore the function and underlying mechanism of STRIP2 in LUAD.MethodsExpression of STRIP2 was determined using the Cancer Genome Atlas (TCGA), GTEx, Ualcan, and the Human Protein Altas databases. The Correlation of STRIP2 and survival was detected by PrognoScan and Kaplan-Meier plotter databases. Besides, the correlation between STRIP2 expression and tumor immune infiltration as well as immune checkpoints were analyzed by the ssGSEA method. The biological function of STRIP2 and its co-expression genes was determined by gene ontology (GO) and Genes and Genomes (KEGG), respectively. Finally, the expression level and biological function of STRIP2 in LUAD were determined by qPCR, CCK8, transwell, and wound healing assays.ResultsThis manuscript revealed a significantly increased expression of mRNA and protein of STRIP2 in lung adenocarcinoma compared with the adjacent normal tissues. GEO and Kaplan-Meier plotter databases showed higher STRIP2 expression levels were correlated with poor prognosis survival of LUAD. Moreover, Cox regression analysis suggested that a higher STRIP2 level served as an independent risk factor in predicting deteriorative overall survival (OS) for LUAD patients. SsGSEA results showed STRIP2 expression level was positively correlated with infiltrating levels of Th2 cells in LUAD. Lastly, GO analysis indicated the biological processes were enriched in nuclear division and positive regulation of the cell cycle. KEGG signaling pathway analysis showed STRIP2 was correlated with the MAPK signaling pathway and the TNF signaling pathway. The GSEA database showed that STRIP2 was positively associated with the epithelial-mesenchymal transition, cell cycle, and TNF signaling pathway. The QRT-PCR assay showed that STRIP2 was upregulated in LUAD cell lines. Cell proliferation and migration were inhibited in LUAD by knockdown of STRIP2. Moreover, we confirmed that the TMPO-AS1/let-7c-5p/STRIP2 network regulates STRIP2 overexpression in LUAD and is associated with poor prognosis.ConclusionOur findings indicated that STRIP2 acted as a crucial oncogene in LUAD and was correlated with unfavorable survival and tumor infiltration inflation.
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