title: Autotaxin Expression Is Regulated at the Post-transcriptional Level by the RNA-binding Proteins HuR and AUF1.
abstract: Autotaxin (ATX) is a key enzyme that converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a lysophospholipid mediator that regulates cellular activities through its specific G protein-coupled receptors. The ATX-LPA axis plays an important role in various physiological and pathological processes, especially in inflammation and cancer development. Although the transcriptional regulation of ATX has been widely studied, the post-transcriptional regulation of ATX is largely unknown. In this study, we identified conserved adenylate-uridylate (AU)-rich elements in the ATX mRNA 3'-untranslated region (3'UTR). The RNA-binding proteins HuR and AUF1 directly bound to the ATX mRNA 3'UTR and had antagonistic functions in ATX expression. HuR enhanced ATX expression by increasing ATX mRNA stability, whereas AUF1 suppressed ATX expression by promoting ATX mRNA decay. HuR and AUF1 were involved in ATX regulation in Colo320 human colon cancer cells and the LPS-stimulated human monocytic THP-1 cells. HuR knockdown suppressed ATX expression in B16 mouse melanoma cells, leading to inhibition of cell migration. This effect was reversed by AUF1 knockdown to recover ATX expression or by the addition of LPA. These results suggest that the post-transcriptional regulation of ATX expression by HuR and AUF1 modulates cancer cell migration. In summary, we identified HuR and AUF1 as novel post-transcriptional regulators of ATX expression, thereby elucidating a novel mechanism regulating the ATX-LPA axis.
authors: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, and.
authors: Shuhong
authors: S
authors: Sun
authors: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, and xiaotianzhang@bnu.edu.cn.
authors: Xiaotian
authors: X
authors: Zhang
authors: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, and.
authors: Lin
authors: L
authors: Lyu
authors: the Key Laboratory of Biodiversity Science and Ecological Engineering, Ministry of Education, College of Life Science, Beijing Normal University, Beijing 100875, China.
authors: Xixi
authors: X
authors: Li
authors: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, and.
authors: Siliang
authors: S
authors: Yao
authors: From the Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, and jjzhang@bnu.edu.cn.
authors: Junjie
authors: J
authors: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002465:Cell Movement; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D020871:RNA Stability; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000099189:Lysophospholipase D
chemical_list: D020413:3' Untranslated Regions; D000067780:ELAV-Like Protein 1; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D009363:Neoplasm Proteins; D010727:Phosphoric Diester Hydrolases; D012334:RNA, Neoplasm; D000099189:Lysophospholipase D; C098770:ELAVL1 protein, human; C000593997:Elavl1 protein, mouse; C000630986:HNRNPD protein, human; C000630987:Hnrpd protein, mouse
keywords: AU-rich element RNA-binding protein 1 (AUF1); ELAV-like protein 1 (HuR (human antigen R)); RNA-binding protein; lysophospholipid; post-transcriptional regulation