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.