No abstract

Homeobox (HOX) genes, including HOXA13, are involved in human cancer. We found that HOXA13 expression was associated with glioma grade and prognosis. Bioinformatics analysis revealed that most of the HOXA13-associated genes were enriched in cancer-related signaling pathways and mainly involved in the regulation of transcription. We transfected four glioma cell lines with Lenti-si HOXA13. HOXA13 increased cell proliferation and invasion and inhibited apoptosis. HOXA13 decreased β-catenin, phospho-SMAD2, and phospho-SMAD3 in the nucleus and increased phospho-β-catenin in the cytoplasm. Furthermore, downregulation of HOXA13 in orthotopic tumors decreased tumor growth. We suggest that HOXA13 promotes glioma progression in part via Wnt- and TGF-β-induced EMT and is a potential diagnostic biomarker for glioblastoma and an independent prognostic factor in high-grade glioma.

Glioblastoma (GBM) is associated with disproportionately high morbidity and mortality, reflecting the need to develop new diagnostic and therapeutic targets for this disease. Recently, accumulating evidence has suggested that small nucleolar RNAs (snoRNAs) are gaining prominence and are more actively involved in tumorigenesis than previously thought. However, no report concerning the implication of snoRNAs in glioma has been published to date. In our study, SNORD76 was first found to be inversely associated with Hox Transcript Antisense Intergenic RNA (HOTAIR) knockdown, and surprisingly, forcibly expressed SNORD76 inhibited proliferation and growth of glioma cells. Moreover, downregulation of SNORD76 led to a more malignant phenotype. The pleiotropy of SNORD76 overexpression could be achieved at least partially through inducing cell cycle arrest at S phase by affecting the Rb-associated cell cycle regulation. Enforced SNORD76 expression in orthotopic tumors resulted in decreased tumor growth and the reduction of tumor volume. Additionally, in surgically resected glioma tissues, SNORD76, not its host gene, was associated with the WHO classification and was selectively downregulated in GBM (WHO grade IV). Collectively, our study adds to a growing body of evidence for the participation of snoRNAs in gliomagenesis and is the first to implicate a snoRNA in glioblastoma.