Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer

Abstract

Aberrant protein O-GlcNAcylation may contribute to the development and malignant behavior of many cancers. This modification is controlled by O-linked β-N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA). The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. The level of OGT and OGA proteins was analyzed by Western blot. A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). An inverse association between OGT and MGEA5 transcripts was determined with regard to prognosis (p < 0.05). In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). No correlations with other parameters were noted, but the results showed a trend of more advanced tumors to be more frequently OGT and OGA positive. The results suggest that increased O-GlcNAcylation may have an effect on tumor aggressiveness and prognosis in laryngeal cancer.

O‐GlcNAcylation in oral squamous cell carcinoma

“…A lack of enhanced O ‐GlcNAc levels or OGT overexpression in OSCC or oral cancer cells suggests that PTM by O ‐GlcNAcylation may not be involved in oral carcinogenesis. These results were inconsistent with hyper‐ O ‐GlcNAcylation and OGT overexpression in squamous cell carcinoma of the larynx, the esophagus, and the skin, suggesting distinct tissue‐specific PTMs. However, our findings are still similar to no differences in O ‐GlcNAc immunostaining intensities between liver or pancreatic cancer and their adjacent normal tissues .…”

Silencing β-linked N-acetylglucosamine transferase induces apoptosis in human gastric cancer cells through PUMA and caspase-3 pathways

“…Additionally, it demonstrated that O-GlcNAcylation enhanced cell growth and invasion, and may play important roles in lung and colon cancer formation and progression (6). In laryngeal cancer, OGT and O-GlcNAcase (OGA) mRNA level was related to larger tumor size, nodal metastases, higher grader and tumor size, their protein level showed a trend of more advanced tumors to be more frequently OGT and OGA positive, suggesting that O-GlcNAcylation may have an effect on tumor aggressiveness (7).…”

Ubiquitination‑deubiquitination in the Hippo signaling pathway (Review)

“…This indicates a methylation-dependent checkpoint in the Hippo pathway. O-GlcNAcylation, catalyzed by O-GlcNAc transferase (87), is a notable type of post-translational modification and has been associated with tumorigenesis by mediating signal transduction, transcription, metabolism and other cellular functions (88)(89)(90). In a recent study, researchers reported that O-GlcNAcylation of YAP at Thr241 within the WW domain is responsible for high-glucose-induced liver oncogenesis (91).…”