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.

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

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.

Study ID	ST002505
Study Title	A Mammalian Conserved Circular RNA CircLARP2 Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism (Part 1)
Study 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
Submit Date	2022-12-06
Raw Data Available	Yes
Raw Data File Type(s)	mzXML
Analysis Type Detail	LC-MS
Release Date	2023-04-03
Release Version	1

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Sample Preparation:

Sampleprep ID:	SP002611
Sampleprep Summary:	The cells were washed with PBS under 37°C and the PBS was removed. 800 μL of cold methanol/acetonitrile (1:1, v/v) to remove the protein and extract the metabolites. The mixture was collected into a new centrifuge tube, and centrifuged at 14000g for 20 min to collect the supernatant. The supernatant was dried in a vacuum centri fuge. For LC MS analysis, the samples were redissolved in 100 μL acetonitrile/water (1:1, v/v) solvent and centrifuged at 14000 g at 4 ℃ for 15 min, then the supernatant was injected.

Sampleprep ID:

SP002611

Sampleprep Summary:

The cells were washed with PBS under 37°C and the PBS was removed. 800 μL of cold methanol/acetonitrile (1:1, v/v) to remove the protein and extract the metabolites. The mixture was collected into a new centrifuge tube, and centrifuged at 14000g for 20 min to collect the supernatant. The supernatant was dried in a vacuum centri fuge. For LC MS analysis, the samples were redissolved in 100 μL acetonitrile/water (1:1, v/v) solvent and centrifuged at 14000 g at 4 ℃ for 15 min, then the supernatant was injected.