GEO series

TMEM97 is A Cholesterol Sensing Onco-Protein and Sustains Mitochondrial Energetics Through Lipid Biosynthesis

GSE312758 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2026/06/15 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 24 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: Homo sapiens (human)
Samples: 24 samples: 8 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
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)

Despite advanced therapeutics, gastric carcinoma is still a leading cause of cancer mortality. Investigating metabolic vulnerabilities has become crucial to identify new drug targets and to develop biomarkers for monitoring disease progress. The aim of this study is to investigate the functional role of TMEM97 in the cholesterol metabolism and carcinogenesis.

Read the full summary ↓

We demonstrated that TMEM97 ablation substantially reduced in vitro cell proliferation and impaired tumor growth in xenograft models. Furthermore, TMEM97 deficiency disrupted cholesterol homeostasis. Untargeted metabolomics identified a significant accumulation of the post-lanosterol intermediate follicular fluid meiosis-activating sterol (FF-MAS) in KO cells under both normal and lipoprotein-deficient serum (LPDS) conditions, implying a bottleneck in cholesterol biosynthesis beyond lanosterol. Notably, TMEM97 KO cells showed compensatory upregulation of key regulatory enzymes HMGCR and SQLE, alongside enhanced expression of sterol regulatory element-binding proteins (SREBP1/2), suggesting a regulatory feedback loop. Additionally, the loss of TMEM97 induced broader metabolic reprogramming as multi-omic analysis revealed impaired TCA cycle with altered levels of intermediates, gene expressions and decreased mitochondrial oxygen consumption rate (OCR), particularly under LPDS conditions. Structural analysis revealed a conserved cholesterol recognition/interaction amino acid consensus (CARC) motif in TMEM97, and the deletion of this motif substantially reduced cholesterol binding in vitro. To conclude, TMEM97 senses cholesterol availability and modulates SREBP-mediated transcriptional responses to lipid availability. Loss of TMEM97 impairs post-lanosterol cholesterol biosynthesis, alters lipid profiles, and disrupts mitochondrial bioenergetics. Given its tumorigenic role and druggability, TMEM97 delineated as a novel drug target for gastric carcinoma.

This dataset

Open GSE312758 in finder → Find more human RNA-seq datasets →

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 GSE312758_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 PRJNA1375822 and SRA study SRP651847. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

8 conditions, mostly in triplicate

Hgc27, FBS, biol ×3 Hgc27, LPDS, biol ×3 Hgc27,SGCTRL, FBS, biol ×3 Hgc27, SGCTRL, LPDS, biol ×3 Hgc27, SG12, FBS, biol ×3 Hgc27, SG12, LPDS, biol ×3 Hgc27, SG21, FBS, biol ×3 Hgc27, SG21, LPDS, biol ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 replicated groups read from 24 sample titles; they account for 24 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM9352611 Hgc27, FBS, biol rep1 Hgc27, FBS, biol
GSM9352612 Hgc27, FBS, biol rep2 Hgc27, FBS, biol
GSM9352613 Hgc27, FBS, biol rep3 Hgc27, FBS, biol
GSM9352614 Hgc27, LPDS, biol rep1 Hgc27, LPDS, biol
GSM9352615 Hgc27, LPDS, biol rep2 Hgc27, LPDS, biol
GSM9352616 Hgc27, LPDS, biol rep3 Hgc27, LPDS, biol
GSM9352617 Hgc27,SGCTRL, FBS, biol rep1 Hgc27,SGCTRL, FBS, biol
GSM9352618 Hgc27,SGCTRL, FBS, biol rep2 Hgc27,SGCTRL, FBS, biol
GSM9352619 Hgc27,SGCTRL, FBS, biol rep3 Hgc27,SGCTRL, FBS, biol
GSM9352620 Hgc27, SGCTRL, LPDS, biol rep1 Hgc27, SGCTRL, LPDS, bi…
GSM9352621 Hgc27, SGCTRL, LPDS, biol rep2 Hgc27, SGCTRL, LPDS, bi…
GSM9352622 Hgc27, SGCTRL, LPDS, biol rep3 Hgc27, SGCTRL, LPDS, bi…
GSM9352623 Hgc27, SG12, FBS, biol rep1 Hgc27, SG12, FBS, biol
GSM9352624 Hgc27, SG12, FBS, biol rep2 Hgc27, SG12, FBS, biol
GSM9352625 Hgc27, SG12, FBS, biol rep3 Hgc27, SG12, FBS, biol
GSM9352626 Hgc27, SG12, LPDS, biol rep1 Hgc27, SG12, LPDS, biol
GSM9352627 Hgc27, SG12, LPDS, biol rep2 Hgc27, SG12, LPDS, biol
GSM9352628 Hgc27, SG12, LPDS, biol rep3 Hgc27, SG12, LPDS, biol
GSM9352629 Hgc27, SG21, FBS, biol rep1 Hgc27, SG21, FBS, biol
GSM9352630 Hgc27, SG21, FBS, biol rep2 Hgc27, SG21, FBS, biol
GSM9352631 Hgc27, SG21, FBS, biol rep3 Hgc27, SG21, FBS, biol
GSM9352632 Hgc27, SG21, LPDS, biol rep1 Hgc27, SG21, LPDS, biol
GSM9352633 Hgc27, SG21, LPDS, biol rep2 Hgc27, SG21, LPDS, biol
GSM9352634 Hgc27, SG21, LPDS, biol rep3 Hgc27, SG21, LPDS, biol

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