LncRNA SELL/L-selectin promotes HPV-positive HNSCC progression and drives fucoidan-me diate d therapeutic strategies
LncRNA SELL/L-selectin promotes HPV-positive HNSCC progression and drives fucoidan-me diate d therapeutic strategies
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DOI：
10.1016/j.actbio.2023.06.011
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发表时间：
2023-07-25
影响因子：
9.7
通讯作者：
Liang，Xinhua
中科院分区：
文献类型：
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作者：
Wang，Shasha;Pang，Xin;Liang，Xinhua
人乳头瘤病毒（HPV）阳性的头颈部鳞状细胞癌（HNSCC）存在较高的淋巴结转移风险和不良预后。在此，对临床收集的HNSCC组织的先进微阵列分析揭示了HPV+HNSCC中lncRNA SELL的显著上调，并且其过表达与淋巴结转移明显相关。lncRNA SELL可通过增加L-选择素的水平，作为促迁移和促侵袭介质以及M1样肿瘤相关巨噬细胞（TAM）的诱导剂发挥作用。此外，褐藻糖胶作为L-选择素的抑制剂，能明显减弱4-硝基喹啉N-氧化物（4-NQO）诱导的HPV 16 E6/E7转基因小鼠舌损伤的形成。这一结果促使我们同步开发纳米递送平台，以验证岩藻聚糖介导的抗生长和抗转移作用。这项工作突出了lncRNA SELL/L-selectin对促进HPV+HNSCC进展的重要影响，并提出了一种潜在的岩藻多糖介导的治疗策略。然而，治疗方案，包括手术和含铂化疗和放疗，并没有提高5年的总生存率，由于淋巴转移的高趋势。在此，临床HNSCC样本的微阵列证实了lncRNA SELL的致癌意义，其作为M1样TAM诱导剂并通过上调L-选择素促进肿瘤发生。岩藻依聚糖作为L-选择素抑制剂抑制转基因小鼠的舌病变，岩藻依聚糖介导的纳米递送平台抑制HPV+HNSCC生长。本研究强调了lncRNA SELL/L-selectin对促进HPV+HNSCC进展的作用，并提出了一种潜在的岩藻多糖介导的治疗方法。
Positive human papillomavirus (HPV+) head and neck squamous cell carcinoma (HNSCC) presents a higher risk of lymph node metastasis and poor prognosis. Here, advanced microarray analysis of clinically collected HNSCC tissues revealed significant upregulation of the lncRNA SELL in HPV+HNSCC, and its overexpression was obviously associated with lymph node metastasis. The lncRNA SELL could function as a promigratory and proinvasive mediator as well as an inducer of M1-like tumour-associated macrophages (TAM) by increasing the level of L-selectin. Furthermore, fucoidan, as an L-selectin inhibitor, obviously weakened the formation of tongue lesions induced by 4-Nitroquinoline N-oxide (4-NQO) in HPV16 E6/E7 transgenic mice. This result drove us to synchronously develop a nanodelivery platform to verify fucoidan-mediated anti-growth and anti-metastasis effects. This work highlighted the important influence of the lncRNA SELL/L-selectin on promoting HPV+HNSCC progression and proposed a potential fucoidan-mediated therapeutic strategy.Statement of significanceHead and neck squamous cell carcinoma (HNSCC) patients with human papillomavirus (HPV) involvement present a greater risk of lymph node metastasis than HPV negative HNSCC patients. However, treatment protocols, including surgery and platinum-based chemo- and radiotherapy, have not improved the 5-year overall survival due to the high tendency of lymphatic metastasis. Here, microarray of clinical HNSCC samples confirms the oncogenic significance of lncRNA SELL, which acts as an M1-like TAM inducer and promotes tumorigenesis by upregulating L-selectin. Fucoidan, as an L-selectin inhibitor, suppresses tongue lesions in transgenic mice, and a fucoidan-mediated nanodelivery platform inhibits HPV+HNSCC growth. The present study highlights lncRNA SELL/L-selectin on promoting HPV+HNSCC progression and proposes a potential fucoidan-mediated therapeutic.