C17orf75 (Njmu-R1) promotes hepatocellular carcinoma progression: a pan-cancer analysis and experimental validation
TL;DR
C17orf75 plays an important role in LIHC progression by regulating cell cycle progression and EMT, and it may serve as a potential therapeutic target for LIHC.
Abstract
Background Chromosome 17 Open Reading Frame 75 (C17orf75) encodes the protein Njmu-R1 (Protein Njmu-R1),, which is involved in intracellular vesicle trafficking; however, its role in tumor progression remains largely unclear. Methods Public datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) were analyzed to evaluate the expression profile, mutation landscape, and diagnostic and prognostic value of C17orf75. Bioinformatics analyses were subsequently performed to explore its associations with immune infiltration. In addition, functional assays were conducted on Hep3B and MHCC-97H cells, and immunohistochemistry (IHC) was performed on clinical liver hepatocellular carcinoma (LIHC) samples. Results C17orf75 was significantly upregulated in multiple cancer types, particularly in LIHC. Elevated C17orf75 expression was associated with unfavorable prognosis and advanced clinicopathological features in LIHC. Functional enrichment analyses indicated that C17orf75-related genes were involved in cell cycle regulation, DNA replication, and epithelial–mesenchymal transition (EMT). Furthermore, C17orf75 expression was closely correlated with immune infiltration, ferroptosis-related genes, and m6A regulators. Knockdown of C17orf75 inhibited the proliferation, migration, and invasion of LIHC cells. C17orf75 knockdown induced G2-phase arrest without significantly affecting apoptosis. Moreover, knockdown of C17orf75 suppressed EMT. Conclusion C17orf75 plays an important role in LIHC progression by regulating cell cycle progression and EMT, and it may serve as a potential therapeutic target for LIHC.