LINC00313 通过 PTBP1/STIM1 轴抑制鼻咽癌细胞自噬并促进其干性。
LINC00313 suppresses autophagy and promotes stemness of nasopharyngeal carcinoma cells through PTBP1/STIM1 axis.
机构信息
Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, PR China.
Department of Laboratory Medicine, Hunan Provincial People's Hospital, Changsha 410005, Hunan Province, PR China.
出版信息
Radiother Oncol. 2024 Jul;196:110310. doi: 10.1016/j.radonc.2024.110310. Epub 2024 Apr 26.
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a kind of malignant head and neck tumor with high mortality. lncRNAs are valuable diagnostic biomarkers and therapeutic targets for various tumors. This study investigated the effects and mechanism of LINC00313 in nasopharyngeal carcinoma.
METHODS
Cell Counting Kit-8 (CCK-8) and immunohistochemistry were used for assessing cell proliferation. The levels of autophagy-related proteins, and stem cell markers were detected. Immunofluorescence assay was used for LC3 detection. Methylated RNA Immunoprecipitation (meRIP) of LINC00313 in NPC cells was assessed. The localization of LINC00313 was verified by luorescence in situ hybridization (FIHS). The interaction between LINC00313 and the downstream targets were analyzed and confirmed by immunoprecipitation (RIP). Besides, the tumorigenesis roles of LINC00313 were confirmed in tumor growth mice model.
RESULTS
LINC00313 was increased in NPC tissues and cells. LINC00313 knockdown enhanced autophagy, and decreased stemness and cell viability of NPC cells through regulating STIM1. METTL3/IGF2BP1-mediated m6A modification promoted the stabilization and up-regulation of LINC00313. LINC00313 activated AKT/mTOR pathway in NPC cells through PTBP1/STIM1 axis. Moreover, LINC00313 promoted tumor growth and metastasis in xenograft model.
CONCLUSION
Upregulation of LINC00313 suppressed autophagy and promoted stemness of NPC cells through PTBP1/STIM1 axis.
背景
鼻咽癌（NPC）是一种死亡率较高的恶性头颈部肿瘤。lncRNAs 是各种肿瘤有价值的诊断生物标志物和治疗靶点。本研究探讨了 LINC00313 在鼻咽癌中的作用和机制。
方法
使用细胞计数试剂盒-8（CCK-8）和免疫组织化学评估细胞增殖。检测自噬相关蛋白和干细胞标志物的水平。使用免疫荧光测定法检测 LC3。评估 NPC 细胞中 LINC00313 的甲基化 RNA 免疫沉淀（meRIP）。通过荧光原位杂交（FISH）验证 LINC00313 的定位。通过免疫沉淀（RIP）分析和验证 LINC00313 与下游靶标的相互作用。此外，通过肿瘤生长小鼠模型证实了 LINC00313 的致瘤作用。
结果
LINC00313 在 NPC 组织和细胞中增加。LINC00313 敲低通过调节 STIM1 增强 NPC 细胞的自噬，降低干细胞特性和细胞活力。METTL3/IGF2BP1 介导的 m6A 修饰促进 LINC00313 的稳定和上调。LINC00313 通过 PTBP1/STIM1 轴在 NPC 细胞中激活 AKT/mTOR 通路。此外，LINC00313 在异种移植模型中促进肿瘤生长和转移。
结论
LINC00313 的上调通过 PTBP1/STIM1 轴抑制 NPC 细胞的自噬并促进其干细胞特性。
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