Recent studies have shown that the non-enzymatic function of CD73 plays a key role in tumor progression, but this function of CD73 in pancreatic cancer cells has not been studied. Furthermore, little is still known about the mechanisms involved in CD73 regulation in tumors.
Western blot and immunohistochemical assays were used to detect the expression of CD73 and other proteins in pancreatic ductal adenocarcinoma (PDAC). CCK-8 assay was used to investigate cell proliferation. Flow cytometry was used to detect cell cycle stage and apoptosis. Wound healing assay was used to investigate the migration ability. Xenograft mouse model was also used to investigate the interaction between miR-30a-5p and CD73.
Here, we found that CD73 expression was upregulated in pancreatic ductal adenocarcinoma (PDAC) and that its expression correlated with poor prognosis. CD73 knockdown inhibited cell growth and induced G1 phase arrest via the AKT/ERK/cyclin D signaling pathway. We also found that tumor necrosis factor receptor (TNFR) 2 was involved in CD73-induced AKT and ERK signaling pathway activation in PDAC. Further, miR-30a-5p overexpression significantly increased the cytotoxic effect of gemcitabine in pancreatic cancer by directly targeting CD73 mRNA, suggesting that regulation of the miR-30a-5p/CD73 axis may play an important role in the development of gemcitabine resistance in pancreatic cancer.
In summary, this regulatory network of CD73 appears to represent a new molecular mechanism underlying PDAC progression, and the mechanistic interaction between miR-30a-5p, CD73 and TNFR2 may provide new insights into therapeutic strategies for pancreatic cancer.
The authors.
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All authors have declared no conflicts of interest.