Unveiling SNX10: a key player in bladder cancer progression.

Abstract

Background: Bladder cancer (BC) ranks as the tenth most common cancer globally, posing a substantial public health burden. Its incidence exhibits marked geographic and demographic variations, emphasizing the need for tailored research and therapeutic approaches. Current strategies prioritize inhibiting BC cell proliferation and invasion to improve survival outcomes. In this study, analysis of 408 BC samples revealed sorting nexin 10 (SNX10) as a key differentially expressed gene. While SNX10 has been implicated in nutrient metabolism, particularly in lipid and bone metabolism, its mechanistic role in BC progression remains poorly defined.

Methods: To investigate SNX10's function, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated knockdown was performed in BC cell lines (T24 and UMUC3), followed by phenotypic evaluation. A mouse xenograft model was utilized to assess tumor growth under low SNX10 expression. Functional assays, including proliferation, migration, and invasion tests, were conducted alongside quantitative polymerase chain reaction (qPCR) and Western blot analyses. RNA sequencing (RNA-seq) and Western blot were employed to identify downstream targets and pathways regulated by SNX10, with MYBL2 emerging as a candidate gene.

Results: SNX10 knockdown significantly suppressed BC cell proliferation, migration, and invasion (P<0.05). In vivo, tumors with reduced SNX10 expression exhibited a 40-50% decrease in volume and weight compared to controls (P<0.01). Mechanistic studies linked SNX10 to MYBL2, an oncogene that regulates cell cycle progression and transcriptional activity. RNA-seq data demonstrated that silencing SNX10 downregulated MYBL2 and associated signaling pathways (e.g., PI3K/AKT, MAPK), corroborated by reduced MYBL2 protein levels via Western blot.

Conclusions: This study identifies SNX10 as a pivotal oncogene in BC, driving tumor progression through MYBL2-dependent pathways. Suppression of SNX10 markedly attenuates malignant behaviors and tumor growth, highlighting the therapeutic potential of targeting the SNX10-MYBL2 axis. These findings deepen the current understanding of BC pathogenesis and provide a foundation for metabolism-targeted therapies. Further research is warranted on SNX10's role in the tumor microenvironment (TME) and its clinical translatability.