Summary of project PR001542

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001542. The data can be accessed directly via it's Project DOI: 10.21228/M8CM5D This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR001542
Project DOI:doi: 10.21228/M8CM5D
Project Title:A Mammalian Conserved Circular RNA CircLARP2 Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism
Project Summary:Circular RNAs (circRNAs) have emerged as crucial regulators in physiology and human diseases. However, evolutionarily conserved circRNAs with potent functions in cancers are rarely reported. Here, we identified a mammalian conserved circRNA circLARP2 that played critical roles in hepatocellular carcinoma (HCC). With clinical specimens, we found that patients with high circLARP2 levels in HCC had advanced prognostic stage and poor overall survival. CircLARP2 facilitated HCC metastasis and lipid accumulation in HCC cell lines. CircLARP2 was one of the rare ones that were identified in HCC metastasis and conserved in mammals, which enabled further studies with animal models. CircLARP2-deficient mice exhibited reduced metastasis and less lipid accumulation in an induced HCC model. We provided lines of evidence at molecular, cellular, and whole organismal levels, to support that circLARP2 functioned as a protein sponge of AUF1. CircLARP2 sequestered AUF1 from binding to LKB1 mRNA, which led to decreased LKB1 mRNA stability and lower LKB1 protein levels. LKB1 as a kinase promoted the phosphorylation of AMPK and then the phosphorylation of ACC, the rate limiting enzyme of fatty acid synthesis. Knockdown of Lkb1 with AAV8-shLkb1 in mice HCC model also proved that Lkb1 was a key element in the regulation. Through this AUF1-LKB1-AMPK-ACC pathway, circLARP2 promoted HCC metastasis and lipid accumulation.
Institute:University of Science and Technology of China
Last Name:Li
First Name:Jingxin
Address:443 Huangshan Road
Email:ljx0418@mail.ustc.edu.cn
Phone:00-86-0551-63600137

Summary of all studies in project PR001542

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
VersionSamplesDownload
(* : Contains raw data)
ST002395 A Mammalian Conserved Circular RNA CircLARP2 Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism (Part 2) Homo sapiens University of Science and Technology of China MS 2023-04-06 1 6 Uploaded data (170.6M)*
ST002505 A Mammalian Conserved Circular RNA CircLARP2 Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism (Part 1) Homo sapiens University of Science and Technology of China MS* 2023-04-03 1 40 Uploaded data (1.4G)*
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