PHF14 knockdown causes apoptosis by inducing DNA damage and impairing the activity of the damage response complex in colorectal cancer

Abstract

The abnormal expression or mutation of the plant homeodomain finger protein 14 (PHF14), a recently discovered PHD finger protein, has been reported to link to a wide range of disorders, like the aetiology and pathophysiology of multiple malignancies. Its detailed biological functions, however, still remain unclear. Herein, we discovered that PHF14 expression is strongly associated with the gastrointestinal tumor grade and gastrointestinal disorders, especially colorectal cancer (CRC), with high PHF14 expressions indicating a poor prognosis. Additionally, the mutation rate of PHF14 in CRC patients accounts for a striking proportion of 18%. PHF14 is also implicated in the expression of several oncogenes. In vitro, PHF14 was significantly expressed in patient tissues and in various CRC cell lines, and its expression was closely associated with cell proliferation and growth. Knockdown of PHF14 mediated severe DNA damage and activation of the ATR-CHK1-H2A.X pathway, leading to apoptosis. Strikingly, PHF14 interacted with KIF4A and contributes to the formation of BRCA2/Rad51 foci, indicating that PHF14 is a newly discovered factor that may participate in the formation and recruitment of DNA damage response complexes. These impairments, however, could be alleviated by restoring PHF14 expression. Importantly, inhibiting PHF14 expression in CRC cells might reduce carcinogenesis in vivo. In conclusion, PHF14 is necessary for CRC cell proliferation and growth, and therefore, it might be used as a novel biomarker and therapeutic target for the disease.