Wang Minghao, Dong Qianze, Wang Yunjie
Department of Neurosurgery, First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
Department of Pathology, First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
Tumour Biol. 2016 Aug;37(8):11049-55. doi: 10.1007/s13277-016-4949-6. Epub 2016 Feb 20.
Rab23 overexpression has been implicated in several human cancers. However, its biological roles and molecular mechanism in astrocytoma have not been elucidated. The aim of this study is to explore clinical significance and biological roles of Rab23 in astrocytoma. We observed negative Rab23 staining in normal astrocytes and positive staining in 39 out of 86 (45 %) astrocytoma specimens using immunohistochemistry. The positive rate of Rab23 was higher in grades III and IV (56.5 %, 26/46) than grades I + II astrocytomas (32.5 %, 13/40, p < 0.05). Transfection of Rab23 plasmid was performed induced A172 cell proliferation, colony formation, invasion, and migration, while Rab23 depletion with siRNA reduced these abilities of U87 cells. In addition, we found that Rab23 transfection upregulated while its depletion reduced Rac1 activity. Treatment of transfected cells with a Rac1 inhibitor decreased Rac1 activity and invasion. In conclusion, Rab23 serves as an important oncoprotein in human astrocytoma by regulating cell invasion and migration through Rac1 activity.
Rab23的过表达与多种人类癌症有关。然而,其在星形细胞瘤中的生物学作用和分子机制尚未阐明。本研究的目的是探讨Rab23在星形细胞瘤中的临床意义和生物学作用。我们采用免疫组织化学方法观察到,正常星形胶质细胞中Rab23染色呈阴性,而86例星形细胞瘤标本中有39例(45%)呈阳性染色。Rab23在III级和IV级(56.5%,26/46)中的阳性率高于I + II级星形细胞瘤(32.5%,13/40,p < 0.05)。转染Rab23质粒可诱导A172细胞增殖、集落形成、侵袭和迁移,而用小干扰RNA(siRNA)敲低Rab23则降低U87细胞的这些能力。此外,我们发现转染Rab23可上调Rac1活性,而敲低Rab23则降低Rac1活性。用Rac1抑制剂处理转染细胞可降低Rac1活性和侵袭能力。总之,Rab23通过Rac1活性调节细胞侵袭和迁移,在人类星形细胞瘤中起重要的癌蛋白作用。