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.
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Data availability
The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.
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This study was supported by Cangzhou City Key Research and Development Project (Number: 204106118).
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KX is responsible for assays and funding. XD, JW and KW acted as assistants.
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Xu, K., Dai, X., Wu, J. et al. N6-methyladenosine (m6A) reader IGF2BP2 stabilizes HK2 stability to accelerate the Warburg effect of oral squamous cell carcinoma progression. J Cancer Res Clin Oncol 148, 3375–3384 (2022). https://doi.org/10.1007/s00432-022-04093-z
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DOI: https://doi.org/10.1007/s00432-022-04093-z