Autotaxin is a novel target of micro<scp>RNA</scp>‐101‐3p

Lyu, Lin; Zhang, Xiaotian; Zhang, Junjie

doi:10.1002/2211-5463.12608

Cited by 13 publications

(11 citation statements)

References 34 publications

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“…It is found that the RNA-binding proteins HuR and AUF1 directly bind to the ATX mRNA 3’-UTR and influence ATX mRNA stability in Colo320 human colon cancer cells and LPS-stimulated THP-1 human monocytic cells [ 31 ]. microRNA-101-3p (miR-101-3p), a well-known tumor suppressor, inhibits ATX regulation by directly targeting a conserved sequence in the ATX mRNA 3’-UTR [ 32 ]. Recently, we clarified that the RNA methyltransferase NSUN2 could methylate the 3’-UTR of ATX mRNA at cytosine 2756.…”

Section: Mechanisms Of Atx Expression Regulationmentioning

confidence: 99%

The Expression Regulation and Biological Function of Autotaxin

Zhang

Yin

et al. 2021

Cells

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Autotaxin (ATX) is a secreted glycoprotein and functions as a key enzyme to produce extracellular lysophosphatidic acid (LPA). LPA interacts with at least six G protein-coupled receptors, LPAR1-6, on the cell membrane to activate various signal transduction pathways through distinct G proteins, such as Gi/0, G12/13, Gq/11, and Gs. The ATX-LPA axis plays an important role in physiological and pathological processes, including embryogenesis, obesity, and inflammation. ATX is one of the top 40 most unregulated genes in metastatic cancer, and the ATX-LPA axis is involved in the development of different types of cancers, such as colorectal cancer, ovarian cancer, breast cancer, and glioblastoma. ATX expression is under multifaceted controls at the transcription, post-transcription, and secretion levels. ATX and LPA in the tumor microenvironment not only promote cell proliferation, migration, and survival, but also increase the expression of inflammation-related circuits, which results in poor outcomes for patients with cancer. Currently, ATX is regarded as a potential cancer therapeutic target, and an increasing number of ATX inhibitors have been developed. In this review, we focus on the mechanism of ATX expression regulation and the functions of ATX in cancer development.

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Section: Mechanisms Of Atx Expression Regulationmentioning

confidence: 99%

The Expression Regulation and Biological Function of Autotaxin

Zhang

Yin

et al. 2021

Cells

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“…A particularly interesting element in this report was the authors’ demonstration that miR-101-3p out-performed the ability of targeted siRNA against autotaxin to inhibit cell growth/confluence. Since only exogenous miR-101-3p addition was able to inhibit this effect <50%, it shows a more effective outcome using miRNA over siRNA, at least in this example [86].…”

Section: Mirna As a Puppet Master Of Lysophosphatidic Acid Signalimentioning

confidence: 99%

MicroRNA Regulation of the Autotaxin-Lysophosphatidic Acid Signaling Axis

Murph

2019

Cancers

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The revelation that microRNAs (miRNAs) exist within the human genome uncovered an underappreciated mechanism of gene expression. For cells to regulate expression of their genes, miRNA molecules and argonaute proteins bind to mRNAs and interfere with efficient translation of the RNA transcript. Although miRNAs have important roles in normal tissues, miRNAs may adopt aberrant functions in malignant cells depending on their classification as either a tumor suppressor or oncogenic miRNA. Within this review, the current status of miRNA regulation is described in the context of signaling through the lysophosphatidic acid receptors, including the lysophosphatidic acid-producing enzyme, autotaxin. Thus far, research has revealed miRNAs that increase in response to lysophosphatidic acid stimulation, such as miR-21, miR-30c-2-3p, and miR-122. Other miRNAs inhibit the translation of lysophosphatidic acid receptors, such as miR-15b, miR-23a, and miR200c, or proteins that are downstream of lysophosphatidic acid signaling, such as miR-146 and miR-21. With thousands of miRNAs still uncharacterized, it is anticipated that the complex regulation of lysophosphatidic acid signaling by miRNAs will continue to be elucidated. RNA-based therapeutics have entered the clinic with enormous potential in precision medicine. This exciting field is rapidly emerging and it will be fascinating to witness its expansion in scope.

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“…However, it remains to be explored whether modulation of ATX expression is involved in the physiologic and metabolic actions of these miRNAs. A TargetScan screen followed by testing in cancer cells also revealed that miR-101-3p inhibits ATX expression by directly targeting a conserved sequence in the ATX mRNA 3 UTR [71]. It is possible that miR-101-3p mediated ATX regulation also contributes to altered ATX levels during obesity and insulin resistance.…”

Section: Regulation Of Atx and Lpp3 In The Context Of Obesity And Metabolic Diseasementioning

confidence: 99%

Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease

Jose

Kienesberger

2021

IJMS

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Besides serving as a structural membrane component and intermediate of the glycerolipid metabolism, lysophosphatidic acid (LPA) has a prominent role as a signaling molecule through its binding to LPA receptors at the cell surface. Extracellular LPA is primarily produced from lysophosphatidylcholine (LPC) through the activity of secreted lysophospholipase D, autotaxin (ATX). The degradation of extracellular LPA to monoacylglycerol is mediated by lipid phosphate phosphatases (LPPs) at the cell membrane. This review summarizes and interprets current literature on the role of the ATX-LPA-LPP3 axis in the regulation of energy homeostasis, insulin function, and adiposity at baseline and under conditions of obesity. We also discuss how the ATX-LPA-LPP3 axis influences obesity-related metabolic complications, including insulin resistance, fatty liver disease, and cardiomyopathy.

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

Cited by 13 publications

References 34 publications

The Expression Regulation and Biological Function of Autotaxin

The Expression Regulation and Biological Function of Autotaxin

MicroRNA Regulation of the Autotaxin-Lysophosphatidic Acid Signaling Axis

Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease

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