Dataset Information

Expression of HNF4G and its potential functions in lung cancer.

ABSTRACT: The hepatocyte nuclear factor 4 gamma (HNF4G), a member of orphan nuclear receptors, is up-regulated and functions as an oncoprotein in bladder cancer. In the present study, we observed that HNF4G expression was elevated in lung cancer tissues as compared to adjacent normal lung tissues. The expression of HNF4G protein was correlated with the tumor size and the prognosis of patients. Transfection with a small interference RNA (siRNA) targeting HNF4G in two lung cancer cell lines (H358 and H292 cells) significantly inhibited cell proliferation via arresting cells at G1 phase and inducing cell apoptosis. In addition, HNF4G siRNA reduced cell proliferation in a xenograft tumor-bearing model. Moreover, A549 cells, which had relative lower level of HNF4G, were ectopic expressed with HNF4G and treated with an AKT inhibitor (MK-2206). MK-2206 exposure not only attenuated the promoting effects of HNF4G overexpression on cell proliferation and cell cycle progression, but also suppressed the inhibitory effects of HNF4G overexpression on cell apoptosis. These data suggested that AKT signaling pathway was a potential upstream mediator of HNF4G. Collectively, our data indicate that HNF4G exerts as an oncogenic role in lung cancer by promoting cell proliferation and that HNF4G expression is a potential prognosis factor for lung cancer.

SUBMITTER: Wang J

PROVIDER: S-EPMC5915054 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression of HNF4G and its potential functions in lung cancer.

Wang Jingyu J Zhang Jun J Xu Longsheng L Zheng Ying Y Ling Danyan D Yang Zhiping Z

Oncotarget 20171204 26

The hepatocyte nuclear factor 4 gamma (HNF4G), a member of orphan nuclear receptors, is up-regulated and functions as an oncoprotein in bladder cancer. In the present study, we observed that HNF4G expression was elevated in lung cancer tissues as compared to adjacent normal lung tissues. The expression of HNF4G protein was correlated with the tumor size and the prognosis of patients. Transfection with a small interference RNA (siRNA) targeting HNF4G in two lung cancer cell lines (H358 and H292 c ...[more]

PMID: 29719587

Similar Datasets

Project description:BackgroundAminopeptidase N (CD13) is a zinc-binding protease that has functional effects on both cancerogenesis and tumor angiogenesis. Since CD13 is an antigen suitable for molecular targeted therapies (e.g. tTF-NGR induced tumor vascular infarction), we evaluated its impact in NSCLC patients, and tested the effects of the CD13-targeted fusion protein tTF-NGR (truncated tissue factor (tTF) containing the NGR motif: asparagine-glycine-arginine) in vivo in nude mice.MethodsExpression of both CD13 and CD31 was studied in 270 NSCLC patients by immunohistochemistry. Clinical correlations and prognostic effects of the expression profiles were analyzed using univariate and multivariate analyses. In addition, a microarray-based analysis on the basis of the KM plotter database was performed. The in vivo effects of the CD13-targeted fusion protein tTF-NGR on tumor growth were tested in CD1 nude mice carrying A549 lung carcinoma xenotransplants.ResultsCD13 expression in tumor endothelial and vessel associated stromal cells was found in 15% of the investigated samples, while expression in tumor cells was observed in 7%. Although no significant prognostic impact was observed in the full NSCLC study cohort, both univariate and multivariate models identified vascular CD13 protein expression to correlate with poor overall survival in stage III and pN2+ NSCLC patients. Microarray-based mRNA analysis for either adenocarcinomas or squamous cell carcinomas did not reveal any significant effect. However, the analysis of CD13 mRNA expression for all lung cancer histologies demonstrated a positive prognostic effect. In vivo, systemic application of CD13-targeted tissue factor tTF-NGR significantly reduced CD13+ A549 tumor growth in nude mice.ConclusionsOur results contribute a data basis for prioritizing clinical testing of tTF-NGR and other antitumor molecules targeted by NGR-peptides in NSCLC. Because CD13 expression in NSCLC tissues was found only in a specific subset of NSCLC patients, rigorous pre-therapeutic testing will help to select patients for these studies.

Project description:Non‑small‑cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide. The most common subtypes of NSCLC are adenocarcinoma (AC) and squamous cell carcinoma (SCC). However, the pathophysiological mechanisms contributing to AC and SCC are still largely unknown, especially the roles of long non‑coding RNAs (lncRNAs). The present study identified differentially expressed lncRNAs between lung AC and SCC by re‑annotation of NSCLC microarray data analysis profiling. The potential functions of lncRNAs were predicted by using coding‑non‑coding gene co‑expressing network. Reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) was used to investigate lncRNA expression levels in AC cell lines (A549 and L78), SCC cell lines (H226 and H520) and normal cells (NL‑20). Western blotting analysis was used to investigate the protein expression levels in these cell lines. A total of 65 lncRNAs were differentially expressed between AC and SCC including 28 lncRNAs that were downregulated in SCC subtypes compared with those in AC ones, and 37 upregulated lncRNAs in SCC subtypes compared with AC subtypes. Three lncRNAs, sex determining region Y‑box 2 overlapping transcript (SOX2‑OT), NCBP2 antisense RNA 2 (NCBP2‑AS2) and ubiquitin like with PHD and ring finger domains 1 (UHRF1), were predicted to be associated with lung cancer; RT‑qPCR confirmed that SOX2‑OT and NCBP2‑AS2 were associated with lung cancer. Finally, western blot assays demonstrated that there was no difference in β‑catenin and glycogen synthase kinase 3β (GSK‑3β) expression in cancer cells compared with NL‑20, but increased phosphorylated (p‑)β‑catenin and p‑GSK‑3β was detected in lung cancer cell lines compared with NL‑20, particularly in A549 cells. Although these results require further experimental verification, the analysis of lncRNA signatures between AC and SCC has provided insights into the regulatory mechanism of NSCLC development.

Dataset Information

Expression of HNF4G and its potential functions in lung cancer.

Publications

Expression of HNF4G and its potential functions in lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets