An Integrated Transcriptomics and Proteomics Analysis Implicates lncRNA MALAT1 in the Regulation of Lipid Metabolism

Autor: Yan Gao, Ruibing Chen, Zhenwen Zhao, Xinyu Guan, Hao Wang, Yali Zhang, Xiangyang Zhang, Xing Li
Rok vydání: 2020
Předmět:
Proteomics
Small interfering RNA
FASN
fatty acid synthase
DHA
docosahexaenoic acid
AA
arachidonic acid
ACC
acetyl-CoA carboxylase
Biochemistry
Analytical Chemistry
Transcriptome
transcriptomics
Transcription (biology)
Cell Movement
LC–MS/MS
liquid chromatography–tandem mass spectrometry
Gene expression
lipid metabolism
PSs
phosphatidylserines
FA
formic acid
MALAT1
metastasis-associated lung adenocarcinoma transcript 1
Gene knockdown
MALAT1
TG
triglyceride
Liver Neoplasms
qRT-PCR
quantitative real-time polymerase chain reaction
SREBF1
sterol regulatory element-binding protein 1
hepatocellular carcinoma
Cell biology
PGs
phosphatidylglycerols
Gene Expression Regulation
Neoplastic
ChIP
chromatin immunoprecipitation
RAP
RNA antisense purification
Liver
RNA
Long Noncoding
PAs
phosphatidic acids
Carcinoma
Hepatocellular
Biology
KEGG
Kyoto Encyclopedia of Genes and Genomes
Cell Line
SCD
stearoyl-CoA desaturase
Humans
long noncoding RNA
Protein kinase A
Molecular Biology
Cell Proliferation
RAB14
Ras-related protein Rab-14
Wound Healing
PCA
principal component analysis
Research
PUFAs
polyunsaturated fatty acids
FRAP
fluorescence recovery after photobleaching
Lipid metabolism
MUFAs
monounsaturated fatty acids
PIs
phosphatidylinositols
2-NBDG
2-[N-(7-Nitrobenz-2-oxa-1
3-diazol-4-yl)amino]-2-deoxy-D-glucose
AMPK
AMP-activated protein kinase
siRNA
small interfering RNA
lncRNA
long noncoding RNA
SFAs
saturated fatty acids
HCC
hepatocellular carcinoma
MRM
multiple reaction monitoring
Zdroj: Molecular & Cellular Proteomics : MCP
ISSN: 1535-9484
Popis: Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in various cancers, and its overexpression is associated with tumor growth and metastasis. MALAT1 has been recognized as a key player in the regulation of RNA splicing and transcription; however, the landscape of gene expression regulated by MALAT1 remains unclear. In this study, we employed an integrated transcriptomics and proteomics strategy to characterize the alterations in gene expression induced by MALAT1 knockdown in hepatocellular carcinoma (HCC) cells and identified 2662 differentially expressed transcripts and 1149 differentially expressed proteins. Interestingly, downregulation of MALAT1 reduced the abundances of multiple genes in the AMP-activated protein kinase (AMPK) signaling and biosynthesis of unsaturated fatty acids pathways. Further investigation showed that MALAT1 knockdown inhibited glucose uptake and lipogenesis by reducing the expression levels of these lipid metabolism related genes, which contributes to the oncogenic role of MALAT1 in tumor cell proliferation and invasion. This study uncovers the function of MALAT1 in the modulation of cancer lipid metabolism, reveals the underlying molecular mechanism, and further supports the potential therapeutic opportunities for targeting MALAT1 in HCC treatment.
Graphical Abstract
Highlights • Multiomic analysis characterizes MALAT1-regulated gene expression in HCC cells. • MALAT1 knockdown reduces the expression of genes involving in lipid metabolism. • MALAT1 knockdown inhibits glucose uptake and lipogenesis. • MALAT1 promotes HCC cell proliferation and migration through regulating lipid metabolism.
In Brief Here we investigate how long noncoding RNA MALAT1 regulates gene expression in liver cancer cell line using an integrated transcriptomics and proteomics strategy. We show that MALAT1 modulates the expression of multiple genes in the AMP-activated protein kinase signaling and lipid metabolism pathways. Additionally, MALAT1 knockdown inhibits lipogenesis and thereby reduces cancer cell proliferation and invasion. This study uncovers the role of MALAT1 in regulating lipid metabolism and further supports the potential therapeutic opportunities by targeting MALAT1.
Databáze: OpenAIRE
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