Epstein-Barr virus-encoded miR-BART6-3p inhibits cancer cell proliferation through the LOC553103-STMN1 axis
Epstein-Barr virus-encoded miR-BART6-3p inhibits cancer cell proliferation through the LOC553103-STMN1 axis
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Epstein-Barr病毒编码的miR-BART6-3p通过LOC553103-STMN1轴抑制癌细胞增殖
DOI：
10.1096/fj.202000039rr
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发表时间：
2020-04-18
期刊：
影响因子：
4.8
通讯作者：
Guo, Can
中科院分区：
文献类型：
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作者：
Wang, Dan;Zeng, Zhaoyang;Guo, Can
EB病毒（Epstein-Barr virus，EBV）是一种致瘤病毒，可引起鼻咽癌（nasopharyngeal carcinoma，NPC）、胃癌（gastric cancer，GC）等多种人类恶性肿瘤。EBV编码44种成熟的微小（mi）RNA，主要表现出致癌特性并促进癌症进展。然而，我们之前已经发现一种EBV编码的miRNA，即EBV-miR-BART 6 - 3 p，通过抑制转移和侵袭而作为肿瘤抑制因子。在这里，我们报告EBV-miR-BART 6 - 3 p通过靶向和下调长链非编码RNA（lncRNA）LOC 553103来抑制EBV相关癌症、NPC和GC的增殖。通过蛋白质组学分析，我们确定stathmin（STMN 1）受到EBV-miR-BART 6 - 3 p和LOC 553103的影响。此外，通过RNA免疫沉淀和荧光素酶报告基因测定，我们证实了LOC 553103直接结合并稳定STMN 1 mRNA的3 ' UTR区域。这些结果表明，EBV-miR-BART 6 - 3 p/L0 C553103/STMN 1轴调节细胞周期相关蛋白的表达，然后抑制EBV相关的肿瘤细胞增殖。这些发现为新的EBV相关癌症治疗提供了潜在的靶点或策略，并为理解EBV感染相关的致癌作用提供了新的见解。
Epstein-Barr virus (EBV) is a tumorigenic virus that can cause various human malignancies such as nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV encodes 44 mature micro (mi)RNAs, mostly exhibiting oncogenic properties and promoting cancer progression. However, we have previously found that one EBV-encoded miRNA, namely EBV-miR-BART6-3p, acts as a tumor suppressor by inhibiting metastasis and invasion. Here, we report that EBV-miR-BART6-3p inhibits the proliferation of EBV-associated cancers, NPC, and GC, by targeting and downregulating a long non-coding RNA (lncRNA), LOC553103. Through proteomics analysis, we determined that stathmin (STMN1) is affected by EBV-miR-BART6-3p and LOC553103. Further, via RNA immunoprecipitation and luciferase reporter assay, we confirmed that LOC553103 directly binds and stabilizes the 3 ' UTR region of STMN1 mRNA. These results indicate that the EBV-miR-BART6-3p/LOC553103/STMN1 axis regulates the expression of cell cycle-associated proteins, which then inhibit EBV-associated tumor cell proliferation. These findings provide potential targets or strategies for novel EBV-related cancer treatments, as well as contributes new insights into the understanding of EBV infection-related carcinogenesis.