LncRNA TMEM105 Promotes Malignancy via the MYC-Ribosome Biogenesis Axis: A Novel Prognostic Biomarker and Therapeutic Target in Colorectal Cancer

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 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 TMEM105 expression was 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 global protein synthesis. Collectively, these findings establish TMEM105 as a putative oncogenic driver that promotes CRC progression by modulating ribosome biogenesis, potentially in concert with MYC signaling. TMEM105 may therefore serve as a promising prognostic biomarker and novel therapeutic target for advanced colorectal cancer.