# TMEM105 upregulation promotes colorectal cancer malignancy: a novel prognostic biomarker potentially linked to the MYC-Ribosome biogenesis axis

## TL;DR

This study shows that TMEM105 is overactive in colorectal cancer and may help cancer cells grow and spread, making it a potential new target for treatment.

## Contribution

The study identifies TMEM105 as a novel prognostic biomarker in CRC linked to the MYC-Ribosome biogenesis axis.

## Key findings

- TMEM105 is significantly upregulated in CRC and associated with advanced stage and metastasis.
- Inhibiting TMEM105 reduces cancer cell viability, colony formation, and migration while increasing apoptosis.
- TMEM105 is linked to ribosome biogenesis and MYC signaling, with downregulation of ribosomal genes observed.

## Abstract

Transmembrane protein 105 (TMEM105 ) has recently emerged as a potential oncogenic factor in various malignancies, yet its role in colorectal cancer (CRC) remains unclear. In this study, we comprehensively investigated the expression and function of TMEM105 in CRC through an integrated in silico, ex vivo, and in vitro approach. Publicly available datasets (TCGA, GSE41328, and GSE25070) were analyzed to assess TMEM105 transcript expression and its association with clinicopathological features, followed by weighted gene co-expression network analysis to identify relevant biological pathways. The expression levels were further validated via RT‒qPCR in 25 paired CRC and adjacent non-tumorous tissues. Functional assays were performed after siRNA-mediated silencing of TMEM105 in CRC cell lines to evaluate its impact on cell viability, clonogenicity, migration, apoptosis, and pathway-specific gene expression. TMEM105 was significantly upregulated in CRC tissues, and elevated expression levels were correlated with advanced stage (stage IV) and metastasis. Co-expression analysis revealed ribosome biogenesis and MYC signaling as pathways strongly associated with TMEM105. The functional inhibition of TMEM105 reduced cell viability, impaired colony formation, suppressed migration, and promoted apoptosis, accompanied by the downregulation of the ribosomal genes RPL7 and RPS2 and a marked decrease in total protein synthesis. Collectively, these findings establish TMEM105 as a putative oncogenic driver in CRC. Our data reveal a strong correlation between TMEM105 upregulation and the modulation of ribosome biogenesis, a process known to be driven by MYC signaling, which aligns with recent mechanistic evidence in other malignancies.

The online version contains supplementary material available at 10.1186/s12935-025-04156-4.