Long Non-coding RNA FOXP4-AS1 Is An Unfavorable Prognostic Factor And Regulates Proliferation And Apoptosis In Colorectal Cancer

Background: Despite improvements in diagnostics and treatment of colorectal cancer(CRC),it remains the third most common malignancy and the fourth most frequent cause of cancer-related deaths worldwide,with particularly high incidence in Western countries.Recent studies have suggested that long non-coding RNAs(lncRNAs)serve as novel class of regulators of cancer biological processes,including proliferation,apoptosis and metastasis.Materials and methods: By utilizing publicly available lncRNAs expression profiling data and other publicly available lncRNAs expression profiling data,we screened out FOXP4-AS1,whose expression is significantly increased in colorectal cancer(CRC).In this study,bioinformatics analyses and q PCR were performed to investigate the expression of FOXP4-AS1 in CRC samples and CRC cell lines.We inhibited FOXP4-AS1 expression by transfecting FOXP4-AS1 specific si RNA.Cell proliferation was determined by using cell viability,colony formation assay,Flow cytometry and Ethynyl deoxyuridine(Edu).Cell apoptosis was determined by using Flow cytometry.Tumor xenografts in animals and immunohistochemistry(IHC)were performed to evaluated the effect of FOXP4-AS1 in CRC tumor growth in vivo.Results: In this study,we analyzed of TCGA RNA sequencing data and other publicly available microarray data.We found that a novel lncRNA,FOXP4-AS1,which expression was significantly up-regulated in CRC tissues and cell lines,and overexpression of FOXP4-AS1 was positively correlated with an advanced pathological stage and a larger tumor size.Additionally,knockdown of FOXP4-AS1 expression could inhibit cell proliferation and induce cell apoptosis.Further,FOXP4-AS1 knockdown induced a marked increase in the number of cells in the G0/G1 phase and a reduction in the number of cells in the S phase in DLD-1,HT-29 and HCT116 cell lines.Consistently,silencing of FOXP4-AS1 inhibited tumor growth in vivo.These findings suggested that FOXP4-AS1 could play crucial role in CRC progression and might be a potential new bio-marker for patients with CRC.Conclusions: FOXP4-AS1 is significantly up-regulated in CRC tissues.Mechanistic investigations showed that FOXP4-AS1 could regulate KLF2,P15,P21 and P27 expression and affect cell proliferation and apoptosis in CRC.