Summary of Study ST002505

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.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002505
Study TitleA Mammalian Conserved Circular RNA CircLARP2 Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism (Part 1)
Study SummaryCircular 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 NameLi
First NameJingxin
Address443 Huangshan Road
Emailljx0418@mail.ustc.edu.cn
Phone00-86-0551-63600137
Submit Date2022-12-06
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2023-04-03
Release Version1
Jingxin Li Jingxin Li
https://dx.doi.org/10.21228/M8CM5D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN004126 AN004127
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Agilent 1290 Infinity Agilent 1290 Infinity
Column Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um) Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um)
MS Type ESI ESI
MS instrument type Triple TOF Triple TOF
MS instrument name ABI Sciex 6600 TripleTOF ABI Sciex 6600 TripleTOF
Ion Mode POSITIVE NEGATIVE
Units peak area peak area

Chromatography:

Chromatography ID:CH003057
Instrument Name:Agilent 1290 Infinity
Column Name:Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um)
Column Temperature:25℃
Flow Gradient:The gradient was 95% B for 0.5 min and was linearly reduced to 65% in 6.5 min, and then was reduced to 40% in 1 min and kept for 1 min, and then increased to 95% in 0.1 min, with a 3 min
Flow Rate:0.5 mL/min
Solvent A:100% water; 25 mM ammonium acetate; 25 mM ammonium hydroxide
Solvent B:100% acetonitrile
Chromatography Type:HILIC
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