Abstract 4167: MUC3A promotes lung cancer progress via activating NFκB pathway and attenuates radiosensitivity

Abstract

Abstract MUC3A is highly expressed in 40% of lung adenocarcinoma, but its functions and effects on clinical outcomes are not well understood. Tissue microarray of 92 patients' tumor samples from Chinese National Human Genetic Resources Sharing Service Platform indicated that highly expression of MUC3A was associated with poor prognosis, advanced staging and low differentiation. IP-MS and co-IP results revealed that MUC3A interacted with RELA and activated the NFκB pathway via promoting RELA phosphorylation and interfering the binding of RELA to IκB. MUC3A knockdown significantly suppressed cell proliferation and induced G1 arrest via down-regulating cell cycle checkpoints such as CDK2/4/6 and Cyclin D1. MUC3A deficiency increased γ-H2AX phosphorylation and increased radiation-induced DNA double strain breaks. MUC3A knockdown inhibited the BRCA-1/RAD51 pathway and nuclear translocation of P53 and XCRR6, suggesting that MUC3A promote DNA damage repair and attenuate radiation sensitivity. Moreover, MUC3A deficiency induced autophagy in lung cancer cells and increased the protein levels of LC3 II and Beclin-1. MUC3A knockdown significantly suppressed tumor growth in H1975 xenograft model and had a synergistic effect with radiation. Less nuclear translocation of RELA and P53 was also observed in tumor tissue in vivo. Our studies indicated that MUC3A was a potential oncogene and its highly expression was associated with unfavorable clinical outcomes in patients with lung adenocarcinoma, who should be more frequently follow-up, and might benefit less from radiotherapy. Citation Format: Yingming Sun, Chengcheng You, Shijing Ma, Yuan Luo, Yan Gong, Yu Xiao, Junhong Zhang, Conghua Xie. MUC3A promotes lung cancer progress via activating NFκB pathway and attenuates radiosensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4167.