Li Zhen, Li Yan, Li Ya, Ren Kewei, Li Xin, Han Xinwei, Wang Jiaxiang
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
J Biochem Mol Toxicol. 2017 Sep;31(9). doi: 10.1002/jbt.21933. Epub 2017 May 23.
Long non-coding RNA (lncRNA) H19 in tumors played important roles in various biological processes. However, the biological role and molecular mechanism of H19 in breast cancer are unclear. Here, we found that H19 was aberrantly upregulated in human breast tumor tissues and cells. A negative correlation between H19 and miR-152 and positive correlation between H19 and DNMT1 mRNA were observed. Downregulation of H19 and DNMT1 significantly retarded breast cancer cell proliferation and invasion. H19 act as an endogenous sponge by directly binding to miR-152. miR-152 directly targeted DNMT1 and was regulated by H19. Besides, H19 overexpression dramatically relieved the inhibition of miR-152 on DNMT1 expression. miR-152 inhibition and DNMT1 overexpression obviously reversed the inhibitory effects of H19 downregulation on cell proliferation and invasion. In conclusion, H19 promoted proliferation and invasion of breast cancer through the miR-152/DNMT1 axis, providing a novel mechanism about the occurrence and development of breast cancer.
长链非编码RNA（lncRNA）H19在肿瘤的各种生物学过程中发挥着重要作用。然而，H19在乳腺癌中的生物学作用和分子机制尚不清楚。在此，我们发现H19在人乳腺肿瘤组织和细胞中异常上调。观察到H19与miR-152呈负相关，与DNMT1 mRNA呈正相关。H19和DNMT1的下调显著抑制乳腺癌细胞的增殖和侵袭。H19通过直接结合miR-152发挥内源性海绵作用。miR-152直接靶向DNMT1并受H19调控。此外，H19的过表达显著缓解了miR-152对DNMT1表达的抑制作用。miR-152的抑制和DNMT1的过表达明显逆转了H19下调对细胞增殖和侵袭的抑制作用。总之，H19通过miR-152/DNMT1轴促进乳腺癌的增殖和侵袭，为乳腺癌的发生发展提供了一种新机制。
