Autotaxin is a novel target of microRNA‐101‐3p

• Published in: FEBS open bio Vol. 9; no. 4; pp. 707 - 716
• Main Authors: Wang, Yuqin, Lyu, Lin, Zhang, Xiaotian, Zhang, Junjie
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-04-2019; John Wiley and Sons Inc; Wiley
• Subjects: autotaxin; Binding sites; Breast cancer; cancer cell; Cancer therapies; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell proliferation; Conserved sequence; Down-Regulation; Enzymes; Gene Expression Regulation, Neoplastic; Genes; HCT116 Cells; Humans; invasion; Laboratories; Liver cancer; Lysophosphatidic acid; Metastasis; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; migration; miRNA; miR‐101‐3p; Motility; mRNA; Neuroblastoma; Phosphoric Diester Hydrolases - genetics; Phosphoric Diester Hydrolases - metabolism; Plasmids; Post-transcription; proliferation; Signal Transduction - genetics; Tumor suppressor genes; Tumorigenesis; United States > US; China; migration; cancer cell; invasion; proliferation; autotaxin; miR‐101‐3p
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.12608

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.
Autotaxin (ATX) is a key enzyme in the production of lysophosphatidic acid (LPA). The ATX–LPA axis is involved in oncogenesis and cancer progression. Here, we identified ATX as a novel target of microRNA‐101‐3p (miR‐101‐3p). miR‐101‐3p downregulates the expression of ATX by directly targeting a conserved sequence in ATX mRNA 3′UTR, leading to the suppression of cancer cell migration, invasion, and proliferation.