Similar articles

Abstract: lung cancer, which is exacerbated by environmental pollution and tobacco use, has become the most common cause of cancer-related deaths worldwide, with a five-year overall survival rate of only 19% (Siegel et al., 2020; Yang et al., 2020; Yu and Li, 2020). Nearly 85% of lung cancers are non-small cell lung cancers, of which lung adenocarcinoma is the most common subtype accounting for 50% of non-small cell lung cancer cases. At present, radiotherapy is the primary therapeutic modality for lung cancer at different stages, with significant prolongation of survival time (Hirsch et al., 2017; Bai et al., 2019; Shi et al., 2020). Irradiation can generate reactive oxygen species (ROS) through the radiolysis reaction of water and oxygen, cause DNA damage and oxidative stress, and subsequently result in cancer cell death (Kim et al., 2019). Nevertheless, radioresistance seriously hinders the success of treatment for lung cancer, owing to local recurrence and distant metastasis (Huang et al., 2021). Compared with small cell lung cancer, non-small cell lung cancer shows more tolerance to radiotherapy. Therefore, it is of great importance to decipher key mechanisms of radioresistance and identify effective molecular radiosensitizers to improve patient survival.

NEDD8结合酶（E2）UBE2F抑制肺癌细胞凋亡导致其放疗抵抗

[1]BaiYH, YunXJ, XueY, et al., 2019. A novel oncolytic adenovirus inhibits hepatocellular carcinoma growth. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(12):1003-1013.

[2]BohnsackRN, HaasAL, 2003. Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. J Biol Chem, 278(29):26823-26830.

[3]CookJA, GiusD, WinkDA, et al., 2004. Oxidative stress, redox, and the tumor microenvironment. Semin Radiat Oncol, 14(3):259-266.

[4]EnoCO, ZhaoGP, OlberdingKE, et al., 2012. The Bcl-2 proteins NOXA and Bcl-xL co-ordinately regulate oxidative stress-induced apoptosis. Biochem J, 444(1):69-78.

[5]HirschFR, ScagliottiGV, MulshineJL, et al., 2017. Lung cancer: current therapies and new targeted treatments. Lancet, 389(10066):299-311.

[6]HuaW, LiCJ, YangZX, et al., 2015. Suppression of glioblastoma by targeting the overactivated protein neddylation pathway. Neuro Oncol, 17(10):1333-1343.

[7]HuangDT, AyraultO, HuntHW, et al., 2009. E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol Cell, 33(4):483-495.

[8]HuangYM, YangXJ, LuYW, et al., 2021. UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance. Cell Death Differ, 28(2):671-684.

[9]JiaXQ, LiCJ, LiLH, et al., 2019. Neddylation inactivation facilitates FOXO3a nuclear export to suppress estrogen receptor transcription and improve fulvestrant sensitivity. Clin Cancer Res, 25(12):3658-3672.

[10]KimW, LeeS, SeoD, et al., 2019. Cellular stress responses in radiotherapy. Cells, 8(9):1105.

[11]LiLH, WangMS, YuGY, et al., 2014. Overactivated neddylation pathway as a therapeutic target in lung cancer. J Natl Cancer Inst, 106(6):dju083.

[12]ShiXQ, ZhangJY, TianH, et al., 2020. Role of adjuvant (chemo) radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(7):549-559.

[13]SiegelRL, MillerKD, SauerAG, et al., 2020. Colorectal cancer statistics, 2020. CA Cancer J Clin, 70(3):145-164.

[14]SunY, LiH, 2013. Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase. Protein Cell, 4(2):103-116.

[15]TanMJ, GallegosJR, GuQY, et al., 2006. SAG/ROC-SCF^β-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection. Neoplasia, 8(12): 1042-1054.

[16]YangF, LiuWW, ChenH, et al., 2020. Carfilzomib inhibits the growth of lung adenocarcinoma via upregulation of Gadd45a expression. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(1):64-76.

[17]YuH, LiSB, 2020. Role of LINC00152 in non-small cell lung cancer. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(3):179-191.

[18]ZhouLS, JiaLJ, 2020. Targeting protein neddylation for cancer therapy. Adv Exp Med Biol, 1217:297-315.

[19]ZhouLS, ZhangWJ, SunY, et al., 2018. Protein neddylation and its alterations in human cancers for targeted therapy. Cell Signal, 44:92-102.

[20]ZhouLS, JiangYY, LuoQ, et al., 2019a. Neddylation: a novel modulator of the tumor microenvironment. Mol Cancer, 18:77.

[21]ZhouLS, JiangYY, LiuXJ, et al., 2019b. Promotion of tumor-associated macrophages infiltration by elevated neddylation pathway via NF-κB-CCL2 signaling in lung cancer. Oncogene, 38(29):5792-5804.

[22]ZhouLS, ZhuJ, ChenWY, et al., 2020. Induction of NEDD8-conjugating enzyme E2 UBE2F by platinum protects lung cancer cells from apoptosis and confers to platinum-insensitivity. Cell Death Dis, 11(11):975.

[23]ZhouWH, XuJ, LiHM, et al., 2017. Neddylation E2 UBE2F promotes the survival of lung cancer cells by activating CRL5 to degrade NOXA via the K11 linkage. Clin Cancer Res, 23(4):1104-1116.

[24]ZhouWH, XuJ, TanMJ, et al., 2018. UBE2M is a stress-inducible dual E2 for neddylation and ubiquitylation that promotes targeted degradation of UBE2F. Mol Cell, 70(6):1008-1024.e6.