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.

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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

Select appropriate tab below to view additional metadata details:

Project:

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

Subject:

Subject ID:SU002605
Subject Type:Cultured cells
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

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

mb_sample_id local_sample_id Genotype
SA252345L-KO-5_POScircLARP2-deficient
SA252346L-KO-4_POScircLARP2-deficient
SA252347L-KO-3_POScircLARP2-deficient
SA252348L-KO-1_NEGcircLARP2-deficient
SA252349L-KO-4_NEGcircLARP2-deficient
SA252350L-KO-2_POScircLARP2-deficient
SA252351L-KO-5_NEGcircLARP2-deficient
SA252352L-KO-3_NEGcircLARP2-deficient
SA252353L-KO-2_NEGcircLARP2-deficient
SA252354PLC-KO-1_NEGcircLARP2-deficient
SA252355PLC-KO-5_NEGcircLARP2-deficient
SA252356PLC-KO-4_NEGcircLARP2-deficient
SA252357PLC-KO-3_NEGcircLARP2-deficient
SA252358PLC-KO-2_NEGcircLARP2-deficient
SA252359PLC-KO-1_POScircLARP2-deficient
SA252360PLC-KO-2_POScircLARP2-deficient
SA252361PLC-KO-5_POScircLARP2-deficient
SA252362PLC-KO-4_POScircLARP2-deficient
SA252363PLC-KO-3_POScircLARP2-deficient
SA252364L-KO-1_POScircLARP2-deficient
SA252325L-WT-1_NEGWild-type
SA252326L-WT-4_POSWild-type
SA252327L-WT-3_POSWild-type
SA252328L-WT-2_NEGWild-type
SA252329L-WT-4_NEGWild-type
SA252330PLC-WT-1_POSWild-type
SA252331L-WT-5_NEGWild-type
SA252332L-WT-2_POSWild-type
SA252333L-WT-3_NEGWild-type
SA252334L-WT-5_POSWild-type
SA252335PLC-WT-5_POSWild-type
SA252336PLC-WT-4_POSWild-type
SA252337L-WT-1_POSWild-type
SA252338PLC-WT-2_POSWild-type
SA252339PLC-WT-1_NEGWild-type
SA252340PLC-WT-3_POSWild-type
SA252341PLC-WT-2_NEGWild-type
SA252342PLC-WT-5_NEGWild-type
SA252343PLC-WT-4_NEGWild-type
SA252344PLC-WT-3_NEGWild-type
Showing results 1 to 40 of 40

Collection:

Collection ID:CO002598
Collection Summary:Cells were counted, washed with cold PBS abd then flash-frozen in liquid N2
Sample Type:Cultured cells

Treatment:

Treatment ID:TR002617
Treatment Summary:Wild-type and circLARP2-deficient PLC cells with no Special treatment

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.

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

MS:

MS ID:MS003873
Analysis ID:AN004126
Instrument Name:ABI Sciex 6600 TripleTOF
Instrument Type:Triple TOF
MS Type:ESI
MS Comments:The mobile phase contained A=25 mM ammonium acetate and 25 mM ammonium hydroxide in water and B= acetonitrile. The gr adient 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 reequilibration period employed.
Ion Mode:POSITIVE
  
MS ID:MS003874
Analysis ID:AN004127
Instrument Name:ABI Sciex 6600 TripleTOF
Instrument Type:Triple TOF
MS Type:ESI
MS Comments:The mobile phase contained A=25 mM ammonium acetate and 25 mM ammonium hydroxide in water and B= acetonitrile. The gr adient 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 reequilibration period employed.
Ion Mode:NEGATIVE
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