The Role of WD40-Repeat Protein 62 (MCPH2) in Brain Growth: Diverse Molecular and Cellular Mechanisms Required for Cortical Development
AIM WD40 repeat-containing 62 (WDR62) is a centrosome-associated gene involved in cell cycling and proliferation. However, the role of WDR62 in human malignancies remains unknown. The present study aimed to identify the role, if any, of WDR62 in the pathogenesis of human gastric cancer (GC). METHODS WDR62 expression in 372 cases of human GC and eight GC cell lines was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry and Western blotting. Correlations between WDR62 expression and clinicopathological characteristics, as well as GC prognosis were determined. WDR62 regulation of GC cell proliferation, invasion, migration and cell cycle distribution were studied both in vitro and in vivo. RESULTS WDR62 expression was significantly increased in GC tissues and cell lines and was associated with poor differentiation and prognosis of GC. WDR62 expression was elevated in GC multidrug resistant cells. Suppressing WDR62 significantly decreased cell proliferation and induced G2/M phase arrest of GC cells. Consistently, WDR62 knockdown inhibited gastric carcinogenesis in nude mice. Regulation of Akt/p38-mitogen-activated protein kinase (MAPK)/multidrug resistance gene 1 (MDR1) expression and activation by WDR62 contributed to the chemoresistance of GC cells. WDR62 overexpresses in GC and the suppression of WDR62 inhibits GC cell growth by inducing G2/M cell cycle arrest. CONCLUSION WDR62 may be a novel prognostic marker and a potential chemotherapy target for GC.