Identification and analysis of KRTAP5-1 as a prognostic biomarker for colorectal carcinoma

Despite emerging evidence linking Keratin-associated protein 5-1 (KRTAP5-1) to cancer, its function in colorectal cancer (CRC) remains elusive. We integrated online databases, Western blotting, pathway analyses (KEGG, GO, GSEA), and in vitro assays, including EdU, scratch wound healing, Transwell, Seahorse XF real-time ATP rate analysis, and mitochondrial function evaluations, to explore the role of KRTAP5-1 in CRC. Our findings revealed that KRTAP5-1 expression was significantly elevated in CRC tissues compared with adjacent normal tissues (p < 0.05) and was associated with poor prognosis. Gene enrichment analyses based on public datasets highlighted an association between KRTAP5-1 expression and mitochondrial-related pathways. Knockdown of KRTAP5-1 reduced SLC25A27 expression, while SLC25A27 overexpression partially rescued the inhibitory effects of KRTAP5-1 knockdown on CRC cell proliferation and migration, suggesting a regulatory association between KRTAP5-1 and SLC25A27. Furthermore, KRTAP5-1 modulation affected mitochondrial characteristics and function, as evidenced by alterations in mitochondrial membrane potential, ROS production, mitochondrial dynamics-related proteins, and cellular metabolic profiles determined by Seahorse extracellular flux analysis, including oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Notably, KRTAP5-1 knockdown significantly reduced mitochondrial ATP production, indicating impaired oxidative phosphorylation capacity. These findings suggest that KRTAP5-1 may be associated with CRC progression through SLC25A27-related mitochondrial functional alterations. KRTAP5-1 may serve as a potential prognostic biomarker for CRC, while the KRTAP5-1/SLC25A27 axis may represent a potential molecular mechanism underlying CRC progression through alterations in mitochondrial homeostasis and energy metabolism.