GEO series

TSC/mTORC1 mediates mTORC2/AKT1 signaling in c-MYC-induced murine hepatocarcinogenesis via centromere protein M

GSE275889 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2024/09/15 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 12 samples
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Activated mTORC2/AKT signaling plays a role in hepatocellular carcinoma (HCC). Research has shown that TSC/mTORC1 and FOXO1 are distinct downstream effectors of AKT signaling in liver regeneration and metabolism. However, the mechanisms by which these pathways mediate mTORC2/AKT activation in HCC are not yet fully understood. Amplification and activation of c-MYC is a key molecular event in HCC.

Read the full summary ↓

In this study, we explored the roles of TSC/mTORC1 and FOXO1 as downstream effectors of mTORC2/AKT1 in c-MYC-induced hepatocarcinogenesis. Using various genetic approaches in mice, we found that manipulating the FOXO pathway had minimal impact on c-MYC-induced HCC. In contrast, loss of mTORC2 inhibited c-MYC-induced HCC, an effect that was completely reversed by ablating TSC2, which activated mTORC1. Additionally, we discovered that p70/RPS6 and 4EBP1/eIF4E act downstream of mTORC1, regulating distinct molecular pathways. Notably, the 4EBP1/eIF4E cascade is crucial for cell proliferation and glycolysis in c-MYC-induced HCC. We also identified centromere protein M (CENPM) as a downstream target of the TSC2/mTORC1 pathway in c-MYC-driven hepatocarcinogenesis, and its ablation entirely inhibited c-MYC-dependent HCC formation. Our findings demonstrate that the TSC/mTORC1/CENPM pathway, rather than the FOXO cascade, is the primary signaling pathway regulating c-MYC-driven hepatocarcinogenesis. Targeting CENPM holds therapeutic potential for treating c-MYC-driven HCC.

This dataset

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Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE275889_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1153513 and SRA study SRP529283. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

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+ 12 more — browse all 12 samples with per-sample file links →

Datasets on a similar topic

GSE276215 TSC/mTORC1 mediates mTORC2/AKT1 signaling in c-MYC-induced murine hepatocarcinogenesis via centromere protein M 10 samples shares mtorc1, mtorc2, akt1, tsc, hepatocarcinogenesis, c-myc-induced, centromere, mediates
GSE318879 Non-canonical mTORC1-TFEB activation due to loss of TSC1 determines hepatocyte plasticity and drives cholangiocarcinogenesis 12 samples shares mtorc1, tsc
GSE278790 PDX1 Phosphorylation Mediates Amino Acid-mTORC1 Signaling in Pancreatic β-Cells [RNA-seq] 12 samples shares mtorc1, mediates
GSE301906 Inhibition of GSK3 and TSC2 Mediates the Oncogenic Activity of AKT in Hepatocellular Carcinoma 10 samples shares tsc, mediates
GSE278789 PDX1 Phosphorylation Mediates Amino Acid-mTORC1 Signaling in Pancreatic β-Cells [ChIP-seq] 16 samples shares mtorc1, mediates
GSE273086 The mTORC1-TFE3-NuRD axis mediates pluripotent stem cells fate transition 6 samples shares mtorc1, mediates
GSE270826 AMPK promotes TFEB transcriptional activity through dephosphorylation at both mTORC1-dependent and -independent sites 48 samples shares mtorc1
GSE276261 EOMES safeguards TSC chromatin accessibility by directing BRG1 to TSC-associated loci [RNA-seq] 45 samples shares tsc

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