Alternatively spliced ANLN isoforms synergistically contribute to the progression of head and neck squamous cell carcinoma.
Alternatively spliced ANLN isoforms synergistically contribute to the progression of head and neck squamous cell carcinoma.
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DOI：
10.1038/s41419-021-04063-2
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发表时间：
2021-08-03
影响因子：
9
通讯作者：
Miao S
中科院分区：
文献类型：
--
作者：
Guo E;Mao X;Wang X;Guo L;An C;Zhang C;Song K;Wang G;Duan C;Zhang X;Yang X;Yuan Z;Sun J;Li X;Yang W;Meng H;Miao S
头颈部鳞状细胞癌是一种常见的恶性肿瘤，死亡率高。苯胺肌动蛋白结合蛋白（ANLN）与多种肿瘤的发生有关。然而，ANLN在HNSCC中的表达模式和功能作用仍不清楚。采用临床资料和网络数据库分析ANLN的表达及其与HNSCC患者生存期的关系。在HNSCC组织和细胞系中评估ANLN的两种主要剪接变体的表达。本研究旨在探讨ANLN亚型在体外和体内对HNSCC的功能作用及其相关机制。ANLN高表达者预后差。ANLN转录物的两种主要亚型ANLN-201和ANLN-210在HNSCC组织和细胞系中高度表达。ANLN基因敲除抑制SCC-9细胞的增殖、迁移和侵袭。在机制上，ANLN-201可以与c-Myc相互作用以保持其蛋白质稳定性，从而在HNSCC中发挥致癌作用。ANLN-210可以通过与RNA结合蛋白hnRNPC结合而经由外泌体转移到巨噬细胞。外泌体ANLN-210通过PTEN/PI 3 K/Akt信号通路促进巨噬细胞极化，从而刺激HNSCC的肿瘤生长。ANLN是影响HNSCC患者预后的独立因素。选择性剪接的ANLN异构体在体内外协同促进HNSCC的肿瘤发生，这可能提供ANLN在HNSCC发展中的深入作用和机制。
Head and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin-binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remain to be unclear. Clinical data and online databases were used to analyze the expression of ANLN and its relationship with HNSCC patient survival. Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo. Our study showed that patients with high expression of ANLN had a poor prognosis. The two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration, and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA-binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC. ANLN was an independent prognostic factor in patients with HNSCC. Alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.