NID1 通过激活 WNT 通路促进喉癌干细胞特性。

NID1 promotes laryngeal cancer stemness via activating WNT pathway.

机构信息

Department of Otorhinolaryngology, The Affiliated Qingyuan Hospital(Qingyuan People'sHospital),Guangzhou Medical University, No.35,Yinquan North Road, Qingyuan, Guangdong, 511518, P.R. China.

Department of Geriatrics, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People'sHospital (Guangdong Academy of Medical Sciences), Southern Medical University, No.106, ZhongShan 2nd Road, YueXiu District, Guangzhou, Guangdong, 510080, P.R. China.

出版信息

Biol Direct. 2024 Nov 13;19(1):115. doi: 10.1186/s13062-024-00548-0.

DOI:10.1186/s13062-024-00548-0

PMID:39538332

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11558908/

Abstract

BACKGROUND

Laryngeal cancer (LCA) is one of the most common head and neck squamous cell carcinoma with poor outcome. LCA stem cells are the main reason for LCA therapy resistance and relapse. Understanding the molecular mechanisms of the self-renew of LCA stem cells is critical to develop now targets and strategies for LCA therapy.

METHODS

Q-PCR and western blotting assays were used to determine NID1 level in LCA tissues and normal laryngeal tissues. MTT, colony formation assay, apoptosis assay and animal model were used to investigate the effect of NID1 on radiotherapy resistance. Side population assay and sphere formation assay were used to determine the role of LCA in the self-renew of LCA stem cells.

RESULTS

NID1 was upregulated in LCA tissues, particularly in LCA tissues derived from relapsed patients, and associated with had poor outcome. NID1 knockdown suppressed radiotherapy resistance and the self-renew of LCA stem cells, while NID1 overexpression promoted radiotherapy resistance and the self-renew of LCA stem cells. Further analysis showed that NID1 promotes radiotherapy resistance and the self-renew of LCA stem cells via activating WNT pathway. Moreover, NID1 level was positively correlated with nuclear β-Catenin level in LCA tissues.

CONCLUSION

Our results show that NID1 promotes radiotherapy resistance and the self-renew of LCA stem cells via activating WNT pathway, providing a novel potential target for LCA treatment.

摘要

背景

喉癌（LCA）是最常见的头颈部鳞状细胞癌之一，预后较差。LCA 干细胞是 LCA 治疗耐药和复发的主要原因。了解 LCA 干细胞自我更新的分子机制对于开发 LCA 治疗的新靶点和策略至关重要。

方法

采用 Q-PCR 和 Western blot 检测 LCA 组织和正常喉组织中 NID1 的水平。采用 MTT、集落形成实验、凋亡实验和动物模型研究 NID1 对放疗耐药的影响。采用侧群实验和球体形成实验研究 NID1 在 LCA 干细胞自我更新中的作用。

结果

NID1 在 LCA 组织中上调，特别是在复发性 LCA 患者的组织中，与不良预后相关。NID1 敲低抑制放疗耐药和 LCA 干细胞的自我更新，而 NID1 过表达促进放疗耐药和 LCA 干细胞的自我更新。进一步分析表明，NID1 通过激活 WNT 通路促进放疗耐药和 LCA 干细胞的自我更新。此外，NID1 水平与 LCA 组织中的核 β-Catenin 水平呈正相关。