Molecular mechanism of lncRNA SNHG12 in immune escape of non-small cell lung cancer through the HuR/PD-L1/USP8 axis
作者全名："Huang, Yusheng; Xia, Lei; Tan, Xiangwu; Zhang, Jingyi; Zeng, Weiwei; Tan, Benxu; Yu, Xian; Fang, Wei; Yang, Zhenzhou"
作者地址："[Huang, Yusheng; Xia, Lei; Tan, Xiangwu; Zhang, Jingyi; Zeng, Weiwei; Tan, Benxu; Yu, Xian; Yang, Zhenzhou] Chongqing Med Univ, Affiliated Hosp 2, Dept Canc Ctr, Tianwen Ave 288, Chongqing 400010, Peoples R China; [Fang, Wei] Chongqing Univ, Gorges Hosp, 165 Xincheng Rd, Chongqing 404100, Peoples R China"
通信作者："Yang, ZZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Canc Ctr, Tianwen Ave 288, Chongqing 400010, Peoples R China.; Fang, W (通讯作者)，Chongqing Univ, Gorges Hosp, 165 Xincheng Rd, Chongqing 404100, Peoples R China."
来源：CELLULAR & MOLECULAR BIOLOGY LETTERS
ESI学科分类：MOLECULAR BIOLOGY & GENETICS
关键词：Non-small cell lung cancer; LncRNA SNHG12; PD-L1; USP8; Immune escape; HuR; Peripheral blood mononuclear cells; CD8(+) T
摘要："Background The pivotal role of long noncoding RNAs (lncRNAs) in cancer immune responses has been well established. This study was conducted with the aim of exploring the molecular mechanism of lncRNA small nucleolar RNA host gene 12 (SNHG12) in immune escape of non-small cell lung cancer (NSCLC). Methods Expression of lncRNA SNHG12, programmed cell death receptor ligand 1 (PD-L1), ubiquitin-specific protease 8 (USP8), and human antigen R (HuR) in NSCLC tissues and cells was measured, and their binding relationship was determined. NSCLC cell proliferation and apoptosis were assessed. Peripheral blood mononuclear cells (PBMCs) were co-cultured with NSCLC cells. The ratio of CD8(+) T cells, PBMC proliferation, and inflammatory factors were determined. lncRNA SNHG12 localization was assessed via subcellular fractionation assay. The half-life period of mRNA was determined using actinomycin D. Xenograft tumor models were established to confirm the role of lncRNA SNHG12 in vivo. Results LncRNA SNHG12 was found to be prominently expressed in NSCLC tissues and cells, which was associated with a poor prognosis. Silencing lncRNA SNHG12 resulted in the reduction in proliferation and the promotion of apoptosis of NSCLC cells, while simultaneously increasing PBMC proliferation and the ratio of CD8(+) T cells. Mechanically, the binding of lncRNA SNHG12 to HuR improved mRNA stability and expression of PD-L1 and USP8, and USP8-mediated deubiquitination stabilized the protein level of PD-L1. Overexpression of USP8 or PD-L1 weakened the inhibition of silencing lncRNA SNHG12 on the immune escape of NSCLC. Silencing lncRNA SNHG12 restricted tumor growth and upregulated the ratio of CD8(+) T cells by decreasing USP8 and PD-L1. Conclusion LncRNA SNHG12 facilitated the immune escape of NSCLC by binding to HuR and increasing PD-L1 and USP8 levels."
基金机构：Chongqing Talents Program [CQYC20200303151]; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University 
基金资助正文："Chongqing Talents Program (CQYC20200303151, Z.Y.) and Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University (Grant No. 202007, Z.Y.)."