WD40 repeat-containing 62 overexpression as a novel indicator of poor prognosis for human gastric cancer

Aim: WD40 repeat-containing 62 (WDR62) is a centrosome-associated gene involved in cell cycling and proliferation. However, the role of WDR62 in human malignan- cies 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), immunohisto- chemistry and Western blotting. Correlations between WDR62 expression and clinicopatholog- ical 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 asso- ciated with poor differentiation and prognosis of GC. WDR62 expression was elevated in GC mul- tidrug 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 resis- tance 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.