ASB16-AS1 up-regulated and phosphorylated TRIM37 to activate NF-κB pathway and promote proliferation, stemness, and cisplatin resistance of gastric cancer
ASB16-AS1 up-regulated and phosphorylated TRIM37 to activate NF-κB pathway and promote proliferation, stemness, and cisplatin resistance of gastric cancer
复制标题
DOI：
10.1007/s10120-020-01096-y
复制
发表时间：
2020-06-22
期刊：
影响因子：
7.4
通讯作者：
Ji, Jiafu
中科院分区：
文献类型：
--
作者：
Fu, Tao;Ji, Ke;Ji, Jiafu
长链非编码RNA（lncRNA）ASB 16反义RNA 1（ASB 16-AS 1）被认为是几种癌症类型中的癌基因，但其与GC的关系尚不清楚。TRIM 37（Tripartite motif containing 37）基因在胃癌发生发展中起重要作用，但其与ASB 16-AS 1和TRIM 37调控胃癌发生发展的分子机制尚不清楚。CCK-8法和集落形成实验检测胃癌细胞的增殖能力。通过球体形成实验和流式细胞术分析来评估GC细胞的干细胞样表型。采用荧光素酶报告基因分析、RNA免疫沉淀（RIP）、pulldown和免疫共沉淀（Co-IP）等方法验证RNA分子间的相互作用。ASB 16-AS 1能增强胃癌细胞的增殖能力和干细胞样特征。更重要的是，ASB 16-AS 1在体内促进GC细胞生长。从机制上讲，ASB 16-AS 1通过隔离miR-3918和miR-4676- 3 p来增强TRIM 37的表达。ASB 16-AS 1通过与ATM丝氨酸/苏氨酸激酶（ATM）协同作用，激活NF-κ B（NF-κ B）通路，诱导TRIM 37磷酸化。
Background Long non-coding RNA (lncRNA) ASB16 antisense RNA 1 (ASB16-AS1) is recognized as an oncogene in several cancer types, but its relation to GC is unknown. Tripartite motif containing 37 (TRIM37) has been proven to accelerate the development of gastric cancer (GC), whereas the molecular mechanism assisted ASB16-AS1 and TRIM37 in regulating GC progression remains unclear.Methods Differentially expressed lncRNAs in GC samples were analyzed based on Gene Expression Omnibus (GEO) data. CCK-8 and colony formation assays were applied to determine the proliferative ability of GC cells. Stem cell-like phenotype of GC cells was assessed by sphere formation assay and flow cytometry analysis. Luciferase reporter assay, RNA immunoprecipitation (RIP), pulldown, and co-immunoprecipitation (Co-IP) were performed to verify the interplay of RNA molecules.Results ASB16-AS1 was upregulated in GC samples according to GEO data and qRT-PCR analysis. ASB16-AS1 strengthened the proliferative ability and stem cell-like characteristics in GC cells. More importantly, ASB16-AS1 encouraged GC cell growth in vivo. Mechanistically, ASB16-AS1 strengthened TRIM37 expression by sequestering miR-3918 and miR-4676-3p. ASB16-AS1 activated NF-kappa B (NF-kappa B) pathway by cooperating with ATM serine/threonine kinase (ATM) to induce TRIM37 phosphorylation.Conclusion In summary, ASB16-AS1 exerted oncogenic functions in GC through modulating TRIM37 expression at both mRNA and protein levels.