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Long non-coding RNA FOXP4-AS1 is an unfavourable prognostic factor and regulates proliferation and apoptosis in colorectal cancer.

ABSTRACT: OBJECTIVES:Despite improvements in diagnosis and treatment, colorectal cancer (CRC) remains the third most common malignancy, and fourth-leading cause of cancer-related death worldwide, and has a particularly high incidence in Western countries. Recent studies have suggested that long non-coding RNAs (lncRNAs) compose a novel class of regulators of cancer biological processes, such as proliferation, apoptosis and metastasis. Here, we report that lncRNA FOXP4-AS1 acts as a functional oncogene in CRC pathogenesis. Moreover, we have attempted to investigate the effects of FOXP4-AS1 on tumour progression, both in vitro and in vivo. MATERIALS AND METHODS:In this study, bioinformatic analyses and qPCR were performed to investigate FOXP4-AS1 expression in CRC tissue samples and CRC cell lines. We inhibited FOXP4-AS1 expression via FOXP4-AS1-specific siRNA transfection. Cell proliferation was assessed using cell viability and colony formation assays, as well as by flow cytometry and ethynyl deoxyuridine (Edu) analyses. Apoptosis was assessed using flow cytometry. Animal tumour xenografts were generated, and immunohistochemistry (IHC) was performed to evaluate effects of FOXP4-AS1 on CRC tumour growth in vivo. RESULTS:We found that FOXP4-AS1 was up-regulated in CRC tissues and cell lines and that its overexpression positively correlated with advanced pathological stages and larger tumour size. Additionally, we found that FOXP4-AS1 knockdown inhibited cell proliferation and induced apoptosis. Furthermore, FOXP4-AS1 knockdown induced marked increase in number of cells in G0/G1 phase and reduction in number of cells in S phase, in DLD-1, HT-29 and HCT116 cell lines. Consistent with these findings, FOXP4-AS1 silencing inhibited tumour growth in vivo. CONCLUSION:These findings suggest that FOXP4-AS1 plays a crucial role in CRC progression and may be a new biomarker in patients with CRC.

SUBMITTER: Li J

PROVIDER: S-EPMC6529074 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Long non-coding RNA FOXP4-AS1 is an unfavourable prognostic factor and regulates proliferation and apoptosis in colorectal cancer.

Li Juan J Lian Yifan Y Yan Changsheng C Cai Zeling Z Ding Jie J Ma Zhonghua Z Peng Peng P Wang Keming K

Cell proliferation 20161027 1

<h4>Objectives</h4>Despite improvements in diagnosis and treatment, colorectal cancer (CRC) remains the third most common malignancy, and fourth-leading cause of cancer-related death worldwide, and has a particularly high incidence in Western countries. Recent studies have suggested that long non-coding RNAs (lncRNAs) compose a novel class of regulators of cancer biological processes, such as proliferation, apoptosis and metastasis. Here, we report that lncRNA FOXP4-AS1 acts as a functional onco ...[more]

PMID: 27790757

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Project description:Background: Knowledge about the prognostic role of long noncoding RNA (lncRNA) in colorectal cancer (CRC) is limited. Therefore, we constructed a lncRNA-related prognostic model based on data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Materials and Methods: CRC transcriptome and clinical data were downloaded from the GSE20916 dataset and the TCGA database, respectively. R software was used for data processing and analysis. The differential lncRNA expression within the two datasets was first screened, and then intersections were measured. Cox regression and the Kaplan-Meier method were used to evaluate the effects of various factors on prognosis. The area under the curve (AUC) of the receiver operating characteristic curve and a nomogram based on multivariate Cox analysis were used to estimate the prognostic value of the lncRNA-related model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were applied to elucidate the significantly involved biological functions and pathways. Results: A total of 11 lncRNAs were crossed. The univariate Cox analysis screened out two lncRNAs, which were analyzed in the multivariate Cox analysis. A nomogram based on the two lncRNAs and other clinicopathological risk factors was constructed. The AUC of the nomogram was 0.56 at 3 years and 0.71 at 5 years. The 3-year nomogram model was compared with the ideal model, which showed that some indices of the 3-year model were consistent with the ideal model, suggesting that our model was highly accurate. The GO and KEGG enrichment analyses showed that positive regulation of secretion by cells, positive regulation of secretion, positive regulation of exocytosis, endocytosis, and the calcium signaling pathway were differentially enriched in the two-lncRNA-associated phenotype. Conclusions: A two-lncRNA prognostic model of CRC was constructed by bioinformatics analysis. The model had moderate prediction accuracy. LncRNA BBOX1-AS1 and lncRNA FOXP4-AS1 were identified as prognostic biomarkers.

Dataset Information

Long non-coding RNA FOXP4-AS1 is an unfavourable prognostic factor and regulates proliferation and apoptosis in colorectal cancer.

Publications

Long non-coding RNA FOXP4-AS1 is an unfavourable prognostic factor and regulates proliferation and apoptosis in colorectal cancer.

Similar Datasets

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