Knockdown of COPA, identified by loss-of-function screen, induces apoptosis and suppresses tumor growth in mesothelioma mouse model.
Malignant mesothelioma is a highly aggressive tumor arising from serosal surfaces of the pleura and is triggered by past exposure to asbestos. Currently, there is no widely accepted treatment for mesothelioma. Development of effective drug treatments for human cancers requires identification of therapeutic molecular targets. We therefore conducted a large-scale functional screening of mesothelioma cells using a genome-wide small interfering RNA library. We determined that knockdown of 39 genes suppressed mesothelioma cell proliferation. At least seven of the 39 genes-COPA, COPB2, EIF3D, POLR2A, PSMA6, RBM8A, and RPL18A-would be involved in anti-apoptotic function. In particular, the COPA protein was highly expressed in some mesothelioma cell lines but not in a pleural mesothelial cell line. COPA knockdown induced apoptosis and suppressed tumor growth in a mesothelioma mouse model. Therefore, COPA may have the potential of a therapeutic target and a new diagnostic marker of mesothelioma.
Sudo
Hitomi
H
Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
Tsuji
Atsushi B
AB
Sugyo
Aya
A
Kohda
Masakazu
M
Sogawa
Chizuru
C
Yoshida
Chisato
C
Harada
Yoshi-nobu
YN
Hino
Okio
O
Saga
Tsuneo
T
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020756:Coatomer Protein / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D008654:Mesothelioma / Q000235:genetics*; D051379:Mice; D010997:Pleural Neoplasms / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics
D020756:Coatomer Protein; D034741:RNA, Small Interfering