The Role Of HOXC11 In Colon Cancer

Objective: Homeobox genes encode evolutionarily conserved transcription factors that play critical roles in regulating abnormal development and malignancy of cancers.Recently,up-regulated expresson of HOXC11 gene has been documented and involved in malignancy and tumorigenesis of several cancers.Colorectal cancer(CRC)is one of the most prevailing malignant gastrointestinal cancers around the world and also its incidence and mortality were respectively considered to rank the third and fourth in human cancers.However,the role of HOXC11 in colon cancer remains unknown.This present study aims to elucidate the role of HOXC11 in the development and malignancy of colon cancer.Methods: 1.R language programming was used to analyse the m RNA expression levels of HOXC11 gene and its clinical prognosis date in colon adenocarcinoma tissues based on The Cancer Genome Atlas(TCGA)databases.q RT-PCR analysis was performed to detect the m RNA expression levels of HOXC11 in both five human colon cancer cells and one normal colon cell.2.The two human monoclonal cancer cell lines of SW480 and SW1116 with stable knockout of HOXC11 by CRISPR/Cas9 gene editing system were sucessfully generated.To expore the effect of HOXC11 on human colon cancer cell proliferation and migration,both in vitro and in vivo experiment were respectively performed to detect the generated cells phenotypes,by using MTT assay,cell colony formation assay,cell drug sensitivity,cell migration assay as well as xenograft tumor assay in nude mice.3.The stable knockout of HOXC11 in SW480 cell was subjected to the whole transcriptome sequencing.Bioinformatics method was used to screen differentially expressed genes.Furtherly,the differentially expressed genes were enriched by KEGG pathway.Results: 1.Bioinformatics analysis demonstrated that the m RNA expression levels of HOXC11 gene was significantly highly expressed in colon adenocarcinoma tissues and its overexpression was associated with poor clinical prognosis using TCGA databases.q RT-PCR analysis showed that m RNA expression levels of HOXC11 was significantly higher in colon cancer cell when compared with normal colon cell.2.After knocking out HOXC11 in two monoclonal cancer cell lines SW480 and SW1116,the proliferation and migration of colon cancer cells were weakened in vitro.Furthermore,knockout of HOXC11 attenuates xenograft tumor growth of colon cancer cell in nude mice.However,it had no effect on sensitivity of colon cancer cells to 5-FU,cisplatin,docetaxol,doxorubicin,erastin,RSL3.3.Whole transcriptome sequencing was performed to detect the total m RNA expression levels in SW480 cell with stable knockout of HOXC11.It demonstrated that a total of 166 differentially expressed genes were confirmed,86 genes of which were significantly upregulated and 52 genes were downregulated.The differentially expressed genes were mainly enriched in the Antigen processing and presentation,ECM-receptor interaction,TNF signaling pathways and so on.Conclusion: Bioinformatics analysis showed that the m RNA expression levels of HOXC11 was significantly highly expressed in colon adenocarcinoma tissues and its overexpression was associated with poor clinical prognosis in colon cancer patients.q RT-PCR analysis demonstrated that m RNA expression levels of HOXC11 was significantly higher in colon cancer cell.Both in vitro and in vivo experiments indicated that HOXC11 significantly promoted cell proliferation,migration,so as to play the role of cancerpromoting gene.Although the underlying molecular mechanism by which aberrant HOXC11 expression lead to abnormal development and malignancy remains poorly understood,our findings provides first-hand evidence that HOXC11 functions as a novel oncogene and may serve as a valuable and profound biomarker of colon cancer prognosis.