The Key Laboratory of Cell Proliferation and Regulation Biology Ministry of Education Institute of Cell Biology College of Life Sciences Beijing Normal University China.
FEBS Open Bio. 2019 Mar 1;9(4):707-716. doi: 10.1002/2211-5463.12608. eCollection 2019 Apr.
Autotaxin (ATX), a vital enzyme that generates lysophosphatidic acid (LPA), affects many biological processes, including tumorigenesis, via the ATX-LPA axis. In this study, we demonstrate that microRNA-101-3p (miR-101-3p), a well-known tumor suppressor, downregulates ATX expression at the posttranscriptional level. We found that miR-101-3p inhibits ATX regulation by directly targeting a conserved sequence in the ATX mRNA 3'UTR. Moreover, we observed an inverse correlation between ATX and miR-101-3p levels in various types of cancer cells. ATX is highly expressed in several human cancers. Here, we verified that ATX expression is significantly inhibited by miR-101-3p in U87 and HCT116 cells. ATX downregulation contributed to the suppression of migration, invasion, and proliferation mediated by miR-101-3p; furthermore, the tumor-suppressing activity of miR-101-3p was partially reduced by the addition of LPA in U87 cells. Our data suggest that ATX is a novel target of miR-101-3p.
自分泌酶（ATX）是一种重要的酶，可生成溶血磷脂酸（LPA），通过 ATX-LPA 轴影响许多生物学过程，包括肿瘤发生。在本研究中，我们证明了 microRNA-101-3p（miR-101-3p），一种已知的肿瘤抑制因子，通过在转录后水平下调 ATX 的表达来发挥作用。我们发现 miR-101-3p 通过直接靶向 ATX mRNA 3'UTR 的保守序列来抑制 ATX 调节。此外，我们在各种类型的癌细胞中观察到 ATX 和 miR-101-3p 水平之间存在负相关关系。ATX 在几种人类癌症中高度表达。在这里，我们验证了 miR-101-3p 在 U87 和 HCT116 细胞中显著抑制 ATX 的表达。ATX 下调有助于抑制 miR-101-3p 介导的迁移、侵袭和增殖；此外，在 U87 细胞中添加 LPA 部分降低了 miR-101-3p 的肿瘤抑制活性。我们的数据表明 ATX 是 miR-101-3p 的一个新靶标。
