Long non-coding RNA H19 promotes the proliferation and invasion of breast cancer through upregulating DNMT1 expression by sponging miR-152
Long non-coding RNA H19 promotes the proliferation and invasion of breast cancer through upregulating DNMT1 expression by sponging miR-152
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DOI：
10.1002/jbt.21933
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发表时间：
2017-09-01
影响因子：
3.6
通讯作者：
Wang, Jiaxiang
中科院分区：
文献类型：
--
作者：
Li, Zhen;Li, Yan;Wang, Jiaxiang
肿瘤中的长链非编码RNA（lncRNA）H19在多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。在这里，我们发现 H19 在人类乳腺肿瘤组织和细胞中异常上调。观察到 H19 与 miR-152 之间呈负相关，而 H19 与 DNMT1 mRNA 之间呈正相关。 H19 和 DNMT1 的下调显着延缓了乳腺癌细胞的增殖和侵袭。 H19 通过直接结合 miR-152 充当内源性海绵。 miR-152直接靶向DNMT1并受H19调节。此外，H19过表达显着缓解了miR-152对DNMT1表达的抑制。 miR-152抑制和DNMT1过表达明显逆转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、发展提供了新的机制。
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.