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


CONCLUSIONS
WDR62 may be a novel prognostic marker and a potential chemotherapy target for GC.
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shan
S
Zeng
Yiming
Y
Tao
Jinlin
J
Huang
Sai
S
Zhang
Liangfang
L
Shen
Huixiang
H
Yang
Haiping
H
Pei
Meizuo
M
Zhong
Gewen
G
Zhang
Ting
T
Liu
Ming
M
Zhou
Hong
H
Shen
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000473:pathology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C552527:WDR62 protein, human
Gastric cancer; Prognosis; WDR62