Dataset Information

Decreased expression of the long non-coding RNA SLC7A11-AS1 predicts poor prognosis and promotes tumor growth in gastric cancer.

ABSTRACT: Many lncRNA and mRNA sense-antisense transcripts have been systematically identified in malignant cells. However, the molecular mechanisms of most lncRNA-mRNA pairs in gastric cancer remain largely unknown. We found the gastric cancer-associated lncRNA SLC7A11-AS1 and coding transcript mRNA SLC7A11 in human gastric cancer specimens by microarray. SLC7A11-AS1, antisense to SLC7A11, is significantly down-regulated in gastric cancer and could promote tumor growth in vitro and in vivo. The effects of SLC7A11-AS1 depend on the regulation of SLC7A11 via the ASK1-p38MAPK/JNK signaling pathway. These findings suggest that decreased expression of SLC7A11-AS1 contributes to the progression of gastric cancer and may be a novel diagnostic biomarker and effective therapeutic target in gastric cancer patients.

SUBMITTER: Luo Y

PROVIDER: S-EPMC5762530 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Decreased expression of the long non-coding RNA SLC7A11-AS1 predicts poor prognosis and promotes tumor growth in gastric cancer.

Luo Yajun Y Wang Cheng C Yong Peng P Ye Pengcheng P Liu Zilin Z Fu Zhiming Z Lu Fei F Xiang Wanping W Tan Wang W Xiao Jiangwei J

Oncotarget 20171107 68

Many lncRNA and mRNA sense-antisense transcripts have been systematically identified in malignant cells. However, the molecular mechanisms of most lncRNA-mRNA pairs in gastric cancer remain largely unknown. We found the gastric cancer-associated lncRNA SLC7A11-AS1 and coding transcript mRNA SLC7A11 in human gastric cancer specimens by microarray. SLC7A11-AS1, antisense to SLC7A11, is significantly down-regulated in gastric cancer and could promote tumor growth <i>in vitro</i> and <i>in vivo</i>. ...[more]

PMID: 29348845

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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.

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.

Dataset Information

Decreased expression of the long non-coding RNA SLC7A11-AS1 predicts poor prognosis and promotes tumor growth in gastric cancer.

Publications

Decreased expression of the long non-coding RNA SLC7A11-AS1 predicts poor prognosis and promotes tumor growth in gastric cancer.

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