Summary of Study ST002395

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 IDST002395
Study TitleA Mammalian Conserved Circular RNA CircLARP2 Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism (Part 2)
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, HeFei, AnHui, 230022, China
Emailljx0418@mail.ustc.edu.cn
Phone00-86-0551-63600137
Submit Date2023-03-10
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2023-04-06
Release Version1
Jingxin Li Jingxin Li
https://dx.doi.org/10.21228/M8CM5D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Genotype
SA251716KO-2circLARP2-deficiency
SA251717KO-3circLARP2-deficiency
SA251718KO-1circLARP2-deficiency
SA251713WT-3Wild-type
SA251714WT-2Wild-type
SA251715WT-1Wild-type
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