title: Tumor suppressor gene Oxidored-nitro domain-containing protein 1 regulates nasopharyngeal cancer cell autophagy, metabolism, and apoptosis in vitro.
abstract: Autophagy is a cellular survival mechanism that involves the catabolic degradation of damaged proteins and organelles during stress. It is particularly required for tumor cell survival during starvation and tumorigenesis. NOR1 is a putative tumor suppressor gene. This study investigated in vitro the effects of NOR1 on the regulation of nasopharyngeal carcinoma autophagy, metabolism, and apoptosis. The data showed that acute oxidative stress induced the expression of NOR1 in normal human cells and tumor cells. Restoration of NOR1 expression downregulated basal autophagy, assessed by autophagy marker LC3 conversion and transmission electron microscopy. In NOR1-expressing tumor cells, reduced autophagy inhibited mitochondrial respiration and energy metabolism. Restoration of NOR1 expression in nasopharyngeal carcinoma cells enhanced apoptosis after induction of oxidative stress. NOR1 expression upregulated Bax expression, Bax translocation to the mitochondria, Smac/DIABLO release from the mitochondria, and activation of caspase-9, and -3, and PARP. In contrast, knockdown of NOR1 expression using NOR1 RNAi resulted in an increase in autophagy and attenuated hydrogen peroxide-induced cell death in HeLa cells. In addition, expression of NOR1 significantly inhibited cisplatin-induced autophagy, resulting in increased cisplatin cytotoxicity and apoptosis. These data revealed novel aspects of the interplay between autophagy and apoptosis in nasopharyngeal carcinoma cells, which underlies the tumor suppression function of NOR1. This work may provide novel insights to contribute to the development of a combinatorial therapy for nasopharyngeal carcinoma.
authors.affiliation: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Yi
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yang
authors.forename: Shuping
authors.initials: S
authors.lastname: Peng
authors.forename: James B
authors.initials: JB
authors.lastname: McCarthy
authors.forename: Bo
authors.initials: B
authors.lastname: Xiang
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001343:Autophagy; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006019:Glycolysis; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D061986:MCF-7 Cells; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010085:Oxidative Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D026901:Membrane Transport Proteins; C479458:OSCP1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D006861:Hydrogen Peroxide; D002945:Cisplatin
keywords: Apoptosis; Autophagy; NOR1; Oxidative stress; Tumor suppressor gene