LARP1 drives steatosis to hepatocellular carcinoma progression in MASH mouse models

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 ..., 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).
, # LARP1 drives steatosis to hepatocellular carcinoma progression in MASH mouse models

**Dataset DOI:** **[10.5061/dryad.18931zdb1](https://doi.org/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...,