Histone demethylase PHF8 accelerates the progression of colorectal cancer and can be regulated by miR-488 invitro.

Abstract

Plant homeo domain finger protein 8 (PHF8), as an oncogene, has been highlighted in cancer development and progression. However, its clinical significance and underlying molecular mechanisms in colorectal cancer (CRC) remain to be fully elucidated. In the present study, the role of PHF8 in the progression of CRC was investigated. The mRNA and protein levels of PHF8 in tissues from patients with CRC and cell lines were detected using the reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Cell viability was analyzed using an MTT assay. The targeted genes were predicted using a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Cell migration was evaluated using a Transwell assay. The results demonstrated that the expression of PHF8 was significantly increased in tumor tissues from patients with CRC and was correlated with tumor-node-metastasis stage. In addition, it was found that overexpressed PHF8 was a predictor of poor overall survival rates in patients with CRC. PHF8 loss-of-function significantly inhibited proliferation and migration, and promoted apoptosis of CRC cells. In addition, bioinformatics methods demonstrated that PHF8 was a putative target of microRNA (miR)-488, and miR-488 was able to inhibit the expression of PHF8 in CRC cells. miR-488 loss-of-function showed increased proliferation and migration, and these effects were reversed by sh-PHF8 transfection in CRC cells. In vitro and in vivo experiments revealed that PHF8 accelerated cancer cell growth and migration, confirming the oncogenic role of PHF8 in human CRC. In conclusion, PHF8 and miR-488 may serve as CRC biomarkers for the prediction of clinical outcome and provide a target for the diagnosis and therapy of CRC.