O‐GlcNAcylation promotes colorectal cancer progression by regulating protein stability and potential catcinogenic function of DDX5

Abstract

The RNA helicase p68 (DDX5), a key player in RNA metabolism, belongs to the DEAD box family and is involved in the development of colorectal cancer. Here, we found both DDX5 and O‐GlcNAcylation are up‐regulated in colorectal cancer. In addition, DDX5 protein level is significantly positively correlated with the expression of O‐GlcNAcylation. Although it was known DDX5 protein could be regulated by post‐translational modification (PTM), how O‐GlcNAcylation modification regulated of DDX5 remains unclear. Here we show that DDX5 interacts directly with OGT in the SW480 cell line, which is the only known enzyme that catalyses O‐GlcNAcylation in humans. Meanwhile, O‐GlcNAcylation could promote DDX5 protein stability. The OGT‐DDX5 axis affects colorectal cancer progression mainly by regulating activation of the AKT/mTOR signalling pathway. Taken together, these results indicated that OGT‐mediated O‐GlcNAcylation stabilizes DDX5, promoting activation of the AKT/mTOR signalling pathway, thus accelerating colorectal cancer progression. This study not only reveals the novel functional of O‐GlcNAcylation in regulating DDX5, but also reveals the carcinogenic effect of the OGT‐DDX5 axis in colorectal cancer.

CircLONP2 enhances colorectal carcinoma invasion and metastasis through modulating the maturation and exosomal dissemination of microRNA-17

“…The oncogenic role of DDX5 and DDX17 in CRC progression has been wellestablished, however, the role of DDX1 in CRC progression is not yet clear. It might be more interesting to investigate whether and how DDX1 mediates the prometastasis role of circLONP2 in CRC [28][29][30].…”

CircPRMT5 circular RNA promotes proliferation of colorectal cancer through sponging miR‐377 to induce E2F3 expression

“…Tumour volume and tumour weight were measured. Tumours were collected and prepared for histological examination …”

Endogenous interaction profiling identifies DDX5 as an oncogenic coactivator of transcription factor Fra-1

“…With regards of cancers, DDX5 has a critical role in cancer development [286,287]. The abnormal expression of DDX5 was identified in various cancers, including breast cancer [288], lung cancer [289], colorectal cancer [290,291], colon cancer [292,293], multiple myeloma [294], cutaneous squamous cell carcinoma [295], leukemia [296,297] and head and neck squamous cell carcinoma [298]. Accordingly, DDX5 acts as a transcriptional coregulator for several cancer-associated TFs, such as AR [299], ERα [272,300], tumor suppressor p53 [301], β-catenin [302,303], MyoD [304], Runx2 [305], Notch transcriptional activation complex [306], NF-κB, and signal transducer and activator of transcription 3 (STAT3) [306].…”