LARP1 drives steatosis to hepatocellular carcinoma progression in MASH mouse models
Data files
Jan 27, 2026 version files 11.13 MB
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expt_1_raw_FPKM.csv
784.42 KB
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expt_2_raw_FPKM.csv
4.24 MB
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Log2FC_dyrad_submission.xlsx
6.10 MB
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README.md
6.61 KB
Abstract
Background: This study focuses on the role of an RNA binding protein, La-related protein 1 or LARP1 in progression of metabolic dysfunction–associated steatotic liver disease (MASLD). A knockout mouse model of the S-adenosylmethionine (SAMe) synthetic enzyme, methionine adenosyltransferase 1A (Mat1a-KO) spontaneously develops MASH and progresses to HCC. We discovered that LARP1 is strongly induced in Mat1a KO during the MASH stage (Ramani 2022, PMC8766892). RNA‑sequencing from LARP1‑overexpressing liver cancer cells and from Larp1‑silenced Mat1a KOs revealed that LARP1 regulates mRNAs controlling key metabolic pathways, including peroxisomal β‑oxidation (Sirtuin 5, SIRT5), aerobic glycolysis (c‑MYC), and oxidative phosphorylation/mitochondrial ribosomal proteins (MRPL13, MRPL50, MRPL59). This dataset is bulk RNA sequencing data from the above studies. Our findings from RNA sequencing reveal a novel role for LARP1 in regulating metabolic pathways associated with MASLD progression through its dysregulation of key mRNAs involved in these pathways.
Dataset DOI: 10.5061/dryad.18931zdb1
Description of the data and file structure
The purpose of this RNA sequencing data is to identify mRNA targets of LARP1 that are dysregulated in MASLD mouse models and are reversed when LARP1 is silenced. Two kinds of data are presented. The first experiment shows that forced expression of LARP1 in liver cancer cell lines changes the translationally active polyribosomal fraction of mRNAs. The second experiment silences LARP1 in the Mat1a KO, a MASLD mouse model and demonstrates that this modulates LARP1's mRNA targets in the liver.
Files and variables
File: expt_1_raw_FPKM.csv
Description: This file contains raw Fragments Per Kilobase of transcript per Million mapped reads or FPKM values of each mRNA from polyribosome and non-translating fractions of Huh7 liver cancer cells overexpressing LARP1 or an empty vector
Variables
- Gene Symbol: Gene symbols are the symbol of the gene corresponding to each mRNA.
- Transcripts ID: Transcript ID is the ID of the transcripts or mRNAs encoded by each gene symbol.
- Type: Is the type of molecule, in this case it is messenger RNA or mRNA
- 1_CTRL FPKM: FPKM values of non-translating fraction mRNA obtained from polyribosome profiling of RNA from Huh7 cells transfected with empty vector (EV).
- 2_CTRL FPKM: FPKM values of non-translating fraction mRNA obtained from polyribosome profiling of RNA from Huh7 cells transfected with empty vector (EV).
- 5_CTRL FPKM: FPKM values of polyribosomal fraction mRNA obtained from polyribosome profiling of RNA from Huh7 cells transfected with empty vector (EV)
- 6_CTRL FPKM: FPKM values of polyribosomal fraction mRNA obtained from polyribosome profiling of RNA from Huh7 cells transfected with empty vector (EV)
- C_3 FPKM: FPKM values of non-translating fraction obtained from polyribosome profiling of RNA from Huh7 cells transfected with LARP1 vector (LARP1 OV)
- C_4 FPKM: FPKM values of non-translating fraction obtained from polyribosome profiling of RNA from Huh7 cells transfected with LARP1 vector (LARP1 OV)
- C_7 FPKM: FPKM values of polyribosomal fraction obtained from polyribosome profiling of RNA from Huh7 cells transfected with LARP1 vector (LARP1 OV)
- C_8 FPKM: FPKM values of polyribosomal fraction obtained from polyribosome profiling of RNA from Huh7 cells transfected with LARP1 vector (LARP1 OV)
- 3_4_case Average FPKM: Average FPKM value of two replicates (C_3 FPKM and C_4 FPKM) of non-translating fraction obtained from polyribosome profiling of RNA from Huh7 cells transfected with LARP1 vector (LARP1 OV)
- 5_6_CTRL Average FPKM: Average FPKM value of two replicates (5_CTRL FPKM and 6_CTRL FPKM) of polyribosomal fraction mRNA obtained from polyribosome profiling of RNA from Huh7 cells transfected with empty vector (EV)
- 7_8_case Average FPKM: Average FPKM value of two replicates (C_7 FPKM and C_8 FPKM) of polyribosomal fraction obtained from polyribosome profiling of RNA from Huh7 cells transfected with LARP1 vector (LARP1 OV)
- 1_2_CTRL Average FPKM: Average FPKM value of two replicates (1_CTRL FPKM and 2_CTRL FPKM) of non-translating fraction mRNA obtained from polyribosome profiling of RNA from Huh7 cells transfected with empty vector (EV).
File: expt_2_raw_FPKM.csv
Description: This file contains raw Fragments Per Kilobase of transcript per Million mapped reads or FPKM of mRNAs from livers of wild type (WT), MAT1A KO, and MAT1A KO with Larp1 silencing (Larp1 si). CR1, 2, 3,7,8,9 are WT liver mRNA. CR4,5,6 are MAT1A KO liver mRNA. CR10,11,12,13,14 are MAT1A KO+Larp1 Si liver mRNAs.
Variables
- RNA ID: The accession number of the RNA
- Symbol:Gene symbols are the symbol of the gene corresponding to each mRNA.
- Type: Is the type of molecule, in this case it is messenger RNA or mRNA
- CR1 FPKM: FPKM value of mRNA from WT liver injected with a CAS empty vector
- CR2 FPKM: FPKM value of mRNA from WT liver injected with a CAS empty vector
- CR3 FPKM: FPKM value of mRNA from WT liver injected with a CAS empty vector
- CR4 FPKM: FPKM value of mRNA from Mat1a KO liver
- CR5 FPKM: FPKM value of mRNA from Mat1a KO liver
- CR6 FPKM: FPKM value of mRNA from Mat1a KO liver
- CR7 FPKM: FPKM value of mRNA from WT liver injected with a CAS empty vector
- CR8 FPKM: FPKM value of mRNA from WT liver injected with a CAS empty vector
- CR9 FPKM: FPKM value of mRNA from WT liver injected with a CAS empty vector
- CR10 FPKM: FPKM value of mRNA from Mat1a KO liver injected with Larp1 si vector
- CR11 FPKM: FPKM value of mRNA from Mat1a KO liver injected with Larp1 si vector
- CR12 FPKM: FPKM value of mRNA from Mat1a KO liver injected with Larp1 si vector
- CR13 FPKM: FPKM value of mRNA from Mat1a KO liver injected with Larp1 si vector
- CR14 FPKM: FPKM value of mRNA from Mat1a KO liver injected with Larp1 si vector
File: Log2FC_dyrad_submission.xlsx
Description: This excel file contains the key definitions and the calculatable log2 (fold change) or Log2 (FC) comparing FPKM values of different groups in experiments 1 and 2 using DEGSEQ2 analysis method. Cells in which the values were not calculatable are marked as N/A.
Variables
- Log2FC expt 1:
- EV (polysome/NTR) log2FC: The log of fold change (FC) of polysomal mRNA versus non-translating mRNA fraction from empty vector transfected Huh7 cells.
- LARP1 OV (polysome/NTR) log2FC: The log of fold change (FC) of polysomal mRNA versus non-translating mRNA fraction from LARP1 OV transfected Huh7 cells
- EV (polysome/NTR) P value: P value of comparison of polysome to NTR in EV samples
- LARP1 OV (polysome/NTR) P value P value of comparison of polysome to NTR in LARP1 OV samples
- Log2FC expt 2:
- Mat1a-KO vs. WT (log2 (CASE_1 / CTRL): Log2Fold change of Mat1a KO total liver RNA compared to WT livers.
- Mat1a-KO+Larp1 si vs. WT (log2 (CASE_2 / CTRL): Log2Fold change of Mat1a KO+Larp1 si total liver RNA compared to WT livers.
- Pvalue(CASE_1 / CTRL) - Statistical P value for Mat1a-KO vs WT log2FC
- Pvalue(CASE_2/ CTRL)-Statistical P value for Mat1a-KO+Larp1 si vs. WT log2FC
Code/software
To access CSV or excel files, microsoft excel is needed.
Access information
Other publicly accessible locations of the data:
- None
Data was derived from the following sources:
- Data was derived from RNA sequencing run by BGI Americas Inc. (Cambridge MA) from 2022-2023.
Experiment 1: Total RNA from human Huh7 liver cancer cells overexpressing an empty vector (EV) or a LARP1 vector was subject to polyribosome profiling to separate the actively translating ribosomal fraction and the non-translating fraction (NTR). The NTR and polysome fractions from EV or LARP1 OV groups was submitted for RNA sequencing (BGI Americas Inc.) and Poisson distribution and DEGseq2 analysis was performed on the same using human reference (GCF_000001405.38_GRCh38.p12).
Experiment 2: Total RNA was isolated from the livers of WT (CAS), Mat1a KO, and Mat1a KO mice injected with a Larp1 CRISPR silencing vector (Larp1 si). Bulk RNA sequencing was performed as in experiment 1 and Poisson distribution and DEGseq2 analysis was performed by using mouse reference (Mus_musculus_NCBI_GCF_000001635.27_GRCm39).