长链非编码 RNA FAM225A 通过与 FUS 结合激活 cGAS-STING 信号通路，促进 CENP-N 的表达，从而调控鼻咽癌细胞的进展。
LncRNA FAM225A activates the cGAS-STING signaling pathway by combining FUS to promote CENP-N expression and regulates the progression of nasopharyngeal carcinoma.
机构信息
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
出版信息
Pathol Res Pract. 2022 Aug;236:154005. doi: 10.1016/j.prp.2022.154005. Epub 2022 Jul 3.
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a common malignant tumor and long non-coding RNAs (lncRNAs) are widely involved in NPC development. Nevertheless, the role of lncRNA FAM225A in NPC remain unclear. Here, we evaluated the effect of FAM225A on NPC cell proliferation, migration and epithelial-mesenchymal transition (EMT).
METHODS
Levels of FAM225A and CENP-N in NPC tissues and cells were measured using RT-qPCR. Western blot assessed CENP-N, Snail, E-cadherin, N-cadherin, Vimentin, cGAS and p-STING levels. FAM225A expression was knocked down by sh-FAM225A or overexpressed by pcDNA-FAM225A. RIP and RNA pull-down verified the binding between FAM225A, CENP-N and FUS. Cell proliferation, migration and invasion were evaluated by CCK8, colony formation and transwell assays.
RESULTS
FAM225A and CENP-N expression levels were evaluated in NPC tissues and cell lines. FAM225A knockdown inhibited NPC cell proliferation, migration and EMT. FAM225A stabilized CENP-N mRNA by recruiting FUS. FAM225A activated cGAS-STING by regulating the expression of CENP-N to promote NPC cell proliferation, migration and EMT.
CONCLUSION
FAM225A regulates NPC progression via FUS/CENP-N mediated cGAS-STING signaling pathway, which provides new therapeutic targets for developing new NPC treatments.
背景
鼻咽癌（NPC）是一种常见的恶性肿瘤，长链非编码 RNA（lncRNA）广泛参与 NPC 的发生发展。然而，lncRNA FAM225A 在 NPC 中的作用尚不清楚。在这里，我们评估了 FAM225A 对 NPC 细胞增殖、迁移和上皮间质转化（EMT）的影响。
方法
采用 RT-qPCR 检测 NPC 组织和细胞中 FAM225A 和 CENP-N 的水平。Western blot 检测 CENP-N、Snail、E-cadherin、N-cadherin、Vimentin、cGAS 和 p-STING 水平。用 sh-FAM225A 敲低 FAM225A 表达或用 pcDNA-FAM225A 过表达。RIP 和 RNA 下拉验证 FAM225A、CENP-N 和 FUS 之间的结合。通过 CCK8、集落形成和 Transwell 检测评估细胞增殖、迁移和侵袭。
结果
评估了 NPC 组织和细胞系中 FAM225A 和 CENP-N 的表达水平。FAM225A 敲低抑制 NPC 细胞增殖、迁移和 EMT。FAM225A 通过招募 FUS 稳定 CENP-N mRNA。FAM225A 通过调节 CENP-N 的表达激活 cGAS-STING，从而促进 NPC 细胞增殖、迁移和 EMT。
结论
FAM225A 通过 FUS/CENP-N 介导的 cGAS-STING 信号通路调节 NPC 进展，为开发新的 NPC 治疗方法提供了新的治疗靶点。
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