Int J Biol Sci 2021; 17(10):2523-2536. doi:10.7150/ijbs.59430

Research Paper

MUC3A promotes non-small cell lung cancer progression via activating the NFκB pathway and attenuates radiosensitivity

Yingming Sun1,2#, Xiaoge Sun1,3#, Chengcheng You1,4, Shijing Ma1, Yuan Luo1, Shan Peng1, Fang Tang1, Xiaoli Tian1, Feng Wang1, Zhengrong Huang1,5, Hongnv Yu6, Yu Xiao5,7, Xiaoyong Wang1,8, Junhong Zhang1,8, Yan Gong5,7✉, Conghua Xie1,8✉

1. Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
2. Department of Radiation and Medical Oncology, Affiliated Sanming First Hospital of Fujian Medical University, Sanming, China.
3. Department of Radiation Oncology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
4. Department of Pathology, China Three Gorges University Medical College, Yichang, China.
5. Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
6. Central Laboratory of Xinhua Hospital of Dalian University, Department of Medical Oncology, Xinhua Hospital of Dalian University, Dalian, China.
7. Tumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
8. Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
#These authors contributed equally to this work.

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Citation:
Sun Y, Sun X, You C, Ma S, Luo Y, Peng S, Tang F, Tian X, Wang F, Huang Z, Yu H, Xiao Y, Wang X, Zhang J, Gong Y, Xie C. MUC3A promotes non-small cell lung cancer progression via activating the NFκB pathway and attenuates radiosensitivity. Int J Biol Sci 2021; 17(10):2523-2536. doi:10.7150/ijbs.59430. Available from https://www.ijbs.com/v17p2523.htm

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Abstract

Mucin 3A (MUC3A) is highly expressed in non-small cell lung cancer (NSCLC), but its functions and effects on clinical outcomes are not well understood. Tissue microarray of 92 NSCLC samples indicated that high levels of MUC3A were associated with poor prognosis, advanced staging, and low differentiation. MUC3A knockdown significantly suppressed NSCLC cell proliferation and induced G1/S accumulation via downregulating cell cycle checkpoints. MUC3A knockdown also inhibited tumor growth in vivo and had synergistic effects with radiation. MUC3A knockdown increased radiation-induced DNA double strain breaks and γ-H2AX phosphorylation in NSCLC cells. MUC3A downregulation inhibited the BRCA-1/RAD51 pathway and nucleus translocation of P53 and XCRR6, suggesting that MUC3A promoted DNA damage repair and attenuated radiation sensitivity. MUC3A knockdown also resulted in less nucleus translocation of RELA and P53 in vivo. Immunoprecipitation revealed that MUC3A interacted with RELA and activated the NFκB pathway via promoting RELA phosphorylation and interfering the binding of RELA to IκB. Our studies indicated that MUC3A was a potential oncogene and associated with unfavorable clinical outcomes. NSCLC patients with a high MUC3A level, who should be more frequent follow-up and might benefit less from radiotherapy.

Keywords: MUC3A, NSCLC, NFκB, Radiosensitivity, DNA damage