Department of Otolaryngology Head & Neck Surgery, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Shanxi Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
Biochem Genet. 2024 Jun;62(3):2117-2133. doi: 10.1007/s10528-023-10541-3. Epub 2023 Oct 20.
Recent research has explored the potential use of serum-derived biomarkers in cancer screening, and mounting evidence has illustrated the pivotal roles of long noncoding RNAs (lncRNAs) in regulating laryngeal squamous cell carcinoma (LSCC) progression. LINC02191 is a newly identified lncRNA and no studies have investigated its role in malignant tumors. This study aims to explore the functions and mechanisms of lncRNA LINC02191 in LSCC. LINC02191 was knocked down in LSCC cells using shRNAs for loss-of-function experiments. RT-qPCR revealed that LINC02191 was upregulated in LSCC patients' serum exosomes, tissues and cells. Western blotting and RT-qPCR were implemented for detecting molecular protein and RNA levels. Colony formation, CCK-8, wound healing and Transwell assays were employed for examining LSCC cell malignant behaviors in vitro. A tumor-bearing mouse model (n = 4/group) was established for examining LINC02191 role in vivo. The results showed that LINC02191 silencing hindered LSCC cell proliferation, invasiveness, migration as well as EMT in vitro and impeded tumorigenesis in xenograft mouse model. Luciferase reporter assay was utilized for verifying the interaction between LINC02191, miR-204-5p and RAB22A. Pearson correlation analysis was employed to evaluate their expression correlation in LSCC tissue specimens (N = 30). Mechanistically, LINC02191 upregulated RAB22A by binding to miR-204-5p, and knocking down LINC02191 inhibited PI3K/Akt/mTOR signaling transduction in LSCC cells and tumor-bearing mice. Moreover, RAB22A overexpression reversed LINC02191 depletion-triggered suppression of LSCC cell aggressiveness and inactivation of PI3K/Akt/mTOR signaling. In conclusion, LINC02191 aggravates LSCC by targeting miR-204-5p/RAB22A/PI3K/Akt/mTOR signaling pathway, which indicates that LINC02191 may serve as a promising target for LSCC treatment.
最近的研究探索了血清衍生生物标志物在癌症筛查中的潜在用途，越来越多的证据表明长非编码 RNA（lncRNA）在调节喉鳞状细胞癌（LSCC）进展中的关键作用。LINC02191 是一种新鉴定的 lncRNA，尚无研究探讨其在恶性肿瘤中的作用。本研究旨在探讨 lncRNA LINC02191 在 LSCC 中的功能和机制。使用 shRNA 敲低 LSCC 细胞中的 LINC02191 进行功能丧失实验。RT-qPCR 显示 LINC02191 在 LSCC 患者血清外泌体、组织和细胞中上调。Western blot 和 RT-qPCR 用于检测分子蛋白和 RNA 水平。集落形成、CCK-8、划痕愈合和 Transwell 测定用于体外检测 LSCC 细胞恶性行为。建立荷瘤小鼠模型（每组 n=4）用于体内研究 LINC02191 作用。结果表明，LINC02191 沉默抑制 LSCC 细胞增殖、侵袭、迁移和 EMT 体外，并抑制异种移植小鼠模型中的肿瘤发生。荧光素酶报告测定用于验证 LINC02191、miR-204-5p 和 RAB22A 之间的相互作用。Pearson 相关分析用于评估 LSCC 组织标本中它们的表达相关性（N=30）。机制上，LINC02191 通过与 miR-204-5p 结合而上调 RAB22A，敲低 LINC02191 抑制 LSCC 细胞和荷瘤小鼠中的 PI3K/Akt/mTOR 信号转导。此外，RAB22A 过表达逆转了 LINC02191 耗竭引发的 LSCC 细胞侵袭性抑制和 PI3K/Akt/mTOR 信号失活。总之，LINC02191 通过靶向 miR-204-5p/RAB22A/PI3K/Akt/mTOR 信号通路加重 LSCC，表明 LINC02191 可能成为 LSCC 治疗的有前途的靶点。
