Salameh Ahmad, Fan Xuejun, Choi Byung-Kwon, Zhang Shu, Zhang Ningyan, An Zhiqiang
Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Department of Molecular and Human Genetics Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
Oncotarget. 2017 Jan 24;8(4):6526-6539. doi: 10.18632/oncotarget.14313.
Here we report that the lncRNA LINC00052 expression correlates positively with HER3/ErbB3 levels in breast cancer cells. Gene silencing of LINC00052 diminished both LINC00052 and HER3 expression and reduced cancer cell growth in vitro and in vivo. LINC00052 overexpression promoted cancer cell growth in vitro and in vivo and increased HER3-mediated downstream signaling. Importantly, neutralization of HER3 signaling with HER3 targeting monoclonal antibodies blocked LINC00052 mediated cancer cell proliferation in vitro and tumor growth in vivo, suggesting LINC00052 promoting cancer growth through HER3 signaling. Taken together, our results indicate that high LINC00052 levels predict activation of HER3-mediated signaling, and LINC00052 expression level may serve as a potential biomarker for HER3 targeted antibody cancer therapies.
在此我们报告，lncRNA LINC00052的表达与乳腺癌细胞中的HER3/ErbB3水平呈正相关。LINC00052的基因沉默降低了LINC00052和HER3的表达，并在体外和体内均减少了癌细胞的生长。LINC00052的过表达在体外和体内均促进了癌细胞的生长，并增加了HER3介导的下游信号传导。重要的是，用靶向HER3的单克隆抗体中和HER3信号传导可在体外阻断LINC00052介导的癌细胞增殖，并在体内抑制肿瘤生长，这表明LINC00052通过HER3信号传导促进癌症生长。综上所述，我们的结果表明，高LINC00052水平预示着HER3介导的信号传导激活，并且LINC00052的表达水平可能作为HER3靶向抗体癌症治疗的潜在生物标志物。
