Induction of apoptosis by Hax-1 siRNA in melanoma cells.
HS1-associated protein X-1 (Hax-1) is a novel intracellular protein and recent studies suggested that it is an anti-apoptotic factor in different tumors. Hax-1 expression was upregulated in various metastatic tumors and cancer cell lines, including melanoma. To understand the role of Hax-1 in melanoma development and progression, we constructed Hax-1 short interfering RNA (siRNA) expression vectors to downregulate Hax-1 expression in a human melanoma A375 cell line. One of the two Hax-1 RNA interference (RNAi) constructs significantly reduced melanoma cell viability, which was due to induction of apoptosis in A375 cells. Molecularly, the induced apoptosis through downregulation of Hax-1 expression was mediated by activation of caspase-3 and poly-ADP-ribose polymerase (PARP) enzymatic activity in A375 cells. The data indicate that Hax-1 plays a role in suppression of apoptosis and promotion of melanoma cell growth, suggesting that this Hax-1 siRNA has a therapeutic indication in control of melanoma.
Li
Wen-Bin
WB
Department of Dermatology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, The West Five Road #157, Xi'an, Shaanxi, PR China.
Feng
Jie
J
Geng
Song-Mei
SM
Zhang
Peng-Yu
PY
Yan
Xiao-Ning
XN
Hu
Gang
G
Zhang
Cai-Qing
CQ
Shi
Bing-Jun
BJ
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C104759:HAX1 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3