Wilms tumor 1 associated protein promotes metastasis and chemo-resistance to oxaliplatin by nuclear factor kappa B pathway in gastric cancer

Abstract

Background There is now substantial evidence that epigenetic modifications largely contribute to gastric carcinogenesis and metastasis, causing a large number of tumor-related deaths. N6-methyladenosine(m6A) is a modification that adds a methyl group at the N6 position, and Wilms tumor 1 associated protein (WTAP) is an important methylase of m6A. WTAP has been reported to play a role in a variety of tumors. Results In the present study, we found that WTAP was highly expressed in gastric cancer (GC) tissues and cells and promoted migration/invasion of GC cells. WTAP promoted the expression of B-cell lymphoma-2(bcl-2), inhibited the expression of Bax, increased the protein levels of p-IKKα, p65, p-p65 and p-IκBα, promoted the expression of nuclear factor kappa B (NF-κB) pathway, and mediated the resistance of GC cells to the chemotherapeutic drug oxaliplatin (OPX). Interestingly, the NF-κB pathway-specific inhibitor caffeic acid phenethyl ester (CAPE) eliminated OPX resistance generated by WTAP overexpression cells and essentially reduced it to the level of resistance in their control cells. Conclusions In summary, the WTAP/NF-κB/bcl-2 pathway may be critical in promoting GC cell proliferation and OPX resistance development, providing a potential therapeutic target for GC treatment.