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自分泌酶是 microRNA-101-3p 的一个新靶点。

Autotaxin is a novel target of microRNA-101-3p.

机构信息

The Key Laboratory of Cell Proliferation and Regulation Biology Ministry of Education Institute of Cell Biology College of Life Sciences Beijing Normal University China.

出版信息

FEBS Open Bio. 2019 Mar 1;9(4):707-716. doi: 10.1002/2211-5463.12608. eCollection 2019 Apr.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f22/6443858/509b9d3b5bc6/FEB4-9-707-g001.jpg

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