Ke Xu1, Xiaojuan Dai2, Jiankun Wu2, Kai Wen3. 1. Department of Stomatology Clinic, Cangzhou Central Hospital, Cangzhou, 061000, Hebei, China. xuke9061@vip.sina.com. 2. Department of Stomatology Clinic, Cangzhou Central Hospital, Cangzhou, 061000, Hebei, China. 3. Department of Maxillofacial Surgery, Cangzhou Central Hospital, Cangzhou, 061000, Hebei, China.
Abstract
PURPOSE: The N6-methyladenosine (m6A) has been involved in the regulation of cell proliferation and metastasis in multiple cancers. However, the biological significance of m6A reader IGF2BP2 in oral squamous cell carcinoma (OSCC) and the mechanism of IGF2BP2 itself have not been fully investigated. METHODS: The cellular phenotypes of OSCC cells were determined by CCK-8 and transwell migration assays. The energy metabolism was detected using glucose uptake/lactate production assay and extracellular acidification rate analysis. The molecular interaction was tested by RNA immunoprecipitation assay. RESULTS: Here, results indicated that IGF2BP2 was up-regulated in OSCC and that it acted as a predictor of poor prognosis. IGF2BP2 promoted the proliferation, migration and Warburg effect of OSCC cells in vitro. Mechanistical assays illustrated that IGF2BP2 directly interacted with HK2 mRNA by binding the 3'-UTR m6A site. Moreover, IGF2BP2 positively promoted the stability of HK2 mRNA and thus the protein level of HK2 increased upon IGF2BP2 overexpression. CONCLUSIONS: In conclusion, the IGF2BP2/m6A/HK2 axis accelerated the abnormal energy metabolism of OSCC. Taken together, these findings revealed a novel mechanism by which IGF2BP2 functions in OSCC progression, which may provide new therapy options for OSCC patients.
PURPOSE: The N6-methyladenosine (m6A) has been involved in the regulation of cell proliferation and metastasis in multiple cancers. However, the biological significance of m6A reader IGF2BP2 in oral squamous cell carcinoma (OSCC) and the mechanism of IGF2BP2 itself have not been fully investigated. METHODS: The cellular phenotypes of OSCC cells were determined by CCK-8 and transwell migration assays. The energy metabolism was detected using glucose uptake/lactate production assay and extracellular acidification rate analysis. The molecular interaction was tested by RNA immunoprecipitation assay. RESULTS: Here, results indicated that IGF2BP2 was up-regulated in OSCC and that it acted as a predictor of poor prognosis. IGF2BP2 promoted the proliferation, migration and Warburg effect of OSCC cells in vitro. Mechanistical assays illustrated that IGF2BP2 directly interacted with HK2 mRNA by binding the 3'-UTR m6A site. Moreover, IGF2BP2 positively promoted the stability of HK2 mRNA and thus the protein level of HK2 increased upon IGF2BP2 overexpression. CONCLUSIONS: In conclusion, the IGF2BP2/m6A/HK2 axis accelerated the abnormal energy metabolism of OSCC. Taken together, these findings revealed a novel mechanism by which IGF2BP2 functions in OSCC progression, which may provide new therapy options for OSCC patients.