Effect of HOXA6 on the proliferation, apoptosis, migration and invasion of colorectal cancer cells.

Abstract

Colorectal cancer (CRC) is one of the most common types of tumor worldwide. The morbidity and mortality rates of CRC have increased significantly in adults <50years of age. In the present study, the effects of homeoboxA6(HOXA6) on the proliferation, apoptosis, migration and invasion of CRC cells were investigated. The results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that the expression of HOXA6 in CRC tumor tissue was higher than that in adjacent normal tissue. Appropriate cell lines and plasmids were selected by RT-PCR and western blot analyses, and recombinant plasmids were transfected into Caco2 or HT-29 cells. The results of RT-qPCR and western blot analyses demonstrated that the expression of HOXA6 was effectively enhanced, or inhibited, following transfection. The rate of cell proliferation was measured with cell counting kit-8, colony formation assay and 5-ethynyl‑2'-deoxyuridine assay, apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling and flow cytometry assays, and migration and invasion were evaluated using Transwell and wound-healing assays. The results demonstrated that the upregulation of HOXA6 promoted cell proliferation, migration and invasion, but inhibited apoptosis, whereas the downregulated expression of HOXA6 produced the opposite effects. In addition, the expression levels of apoptosis- and epithelial-mesenchymal transition(EMT)-related proteins were examined. The results of the western blot analysis revealed that the upregulated expression of HOXA6 suppressed the expression of B-cell lymphoma-2 (Bcl-2)-associated Xprotein, caspase-3, poly(ADP-ribose) polymerase and E-cadherin, but promoted the expression of Bcl-2, N-cadherin and Vimentin, whereas the opposite effect was observed in cells with downregulated HOXA6. These results indicated that HOXA6 regulated apoptosis through the Bcl-2 signaling pathway, and regulated migration and invasion through the EMT process. In conclusion, the present study confirmed that HOXA6 was involved in the regulation of CRC, which may inform the development of strategies for the diagnosis and treatment of CRC.