Chen Shuzheng, Shao Chuxiao, Xu Min, Ji Jiansong, Xie Yanru, Lei Yongliang, Wang Xiaoguang
Lishui Central Hospital & Zhejiang University Lishui Hospital Lishui, Zhejiang, China.
Lishui Center for Disease Control and Prevention Lishui, Zhejiang, China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9052-61. eCollection 2015.
There is now considerable evidence supporting the view that macrophage infiltration is playing a critical role in the proliferation and progression of breast cancer but the underlying molecular mechanisms remain largely unknown. To this end, using long non-coding RNA (lncRNA) expression profiling, we examined changes in lncRNA expression in breast cancer cells treated with conditioned medium (CM) from cultured human THP-1 macrophages. We found that treatment with macrophage CM induced the expression of numerous lncRNAs, including urothelial cancer associated 1 (UCA1). Knockdown of UCA1 using shRNA inhibited AKT phosphorylation and abolished invasiveness of tumor cells induced by macrophage CM. Consistent with these results; we further showed that UCA1 level was significantly enhanced in human primary breast tumors and correlated with advanced clinical stage, supporting its role in promoting carcinogenesis and progression of breast cancer. Together, these results suggest that macrophage could promote invasiveness of breast cancer cells by enhancing expression of lncRNA UCA1.
现在有大量证据支持巨噬细胞浸润在乳腺癌增殖和进展中起关键作用这一观点,但潜在的分子机制仍 largely unknown。为此,我们利用长链非编码RNA(lncRNA)表达谱,检测了用培养的人THP-1巨噬细胞的条件培养基(CM)处理的乳腺癌细胞中lncRNA表达的变化。我们发现,巨噬细胞CM处理诱导了众多lncRNAs的表达,包括尿路上皮癌相关1(UCA1)。使用短发夹RNA(shRNA)敲低UCA1可抑制AKT磷酸化,并消除巨噬细胞CM诱导的肿瘤细胞侵袭性。与这些结果一致;我们进一步表明,UCA1水平在人原发性乳腺肿瘤中显著升高,并与晚期临床分期相关,支持其在促进乳腺癌发生和进展中的作用。总之,这些结果表明巨噬细胞可通过增强lncRNA UCA1的表达来促进乳腺癌细胞的侵袭性。