Zhang Xiao-Fei, Tu Rongfu, Li Keke, Ye Pengxiang, Cui Xiaofeng
School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430072, P. R. China.
College of Life Sciences, Wuhan University, Wuhan 430070, P. R. China.
J Cell Biochem. 2017 Oct;118(10):3391-3400. doi: 10.1002/jcb.25995. Epub 2017 May 3.
PTPRJ is known for its antiproliferative role. Loss of heterozygosity (LOH) of PTPRJ has frequently been observed in various human cancers including colorectal cancer (CRC), lung cancer, and breast cancer. However, the function and mechanism of PTPRJ in CRC are not well understood. At the present study, we show that ectopic expression of PTPRJ inhibits cell growth, migration, and invasiveness in CRC cell line HCT116. Moreover, PTPRJ inhibits the tumorigenecity of HCT116 in a xenograft tumor model. MiR-155, the well-known oncomiR in CRC, is identified as an upstream factor of PTPRJ. MiR-155 directly binds to the 3' untranslated region of PTPRJ mRNA and suppresses the mRNA and protein levels of PTPRJ. Furthermore, the growth-promoting and AKT signaling activation effect of miR-155 was abrogated by PTPRJ overexpression, and vice versa. Our study reveals the crucial role of miR-155/PTPRJ/AKT axis in proliferation and migration of CRC cells and suggests a therapeutic potential of PTPRJ. J. Cell. Biochem. 118: 3391-3400, 2017. © 2017 Wiley Periodicals, Inc.
蛋白酪氨酸磷酸酶受体J（PTPRJ）以其抗增殖作用而闻名。在包括结直肠癌（CRC）、肺癌和乳腺癌在内的多种人类癌症中，经常观察到PTPRJ的杂合性缺失（LOH）。然而，PTPRJ在结直肠癌中的功能和机制尚未完全明确。在本研究中，我们发现PTPRJ的异位表达可抑制结直肠癌细胞系HCT116的细胞生长、迁移和侵袭。此外，在异种移植肿瘤模型中，PTPRJ可抑制HCT116的致瘤性。MiR-155是结直肠癌中著名的致癌miRNA，被确定为PTPRJ的上游因子。MiR-155直接结合PTPRJ mRNA的3'非翻译区，抑制PTPRJ的mRNA和蛋白水平。此外，PTPRJ的过表达消除了miR-155的促生长和AKT信号激活作用，反之亦然。我们的研究揭示了miR-155/PTPRJ/AKT轴在结直肠癌细胞增殖和迁移中的关键作用，并提示了PTPRJ的治疗潜力。《细胞生物化学杂志》118: 3391 - 3400, 2017。© 2017威利期刊公司
