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Loc646329通过海绵吸附miR-21以减少口腔鳞状细胞癌(OSCC)中的RAS/丝裂原活化蛋白激酶信号通路。

Loc646329 sponges miR-21 to reduce RAS/MAP kinase signaling pathway in oral squamous cell carcinoma (OSCC).

作者信息

Adereh Akhtar, Amini Parya, Fateh Azadeh, Faghihkhorasani Ferdos, Khdakarim Nastaran, Marashi Seyed Mehdi, Ahadi Shana, Nayebzadeh Parnian, Khanmirzaei Amir

机构信息

Yasuj University of Medical Science, Yasuj, Iran.

Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec 14. doi: 10.1007/s00210-024-03671-x.

Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive form of head and neck cancer. Emerging evidence suggests that microRNAs (miRNAs) play a crucial role in the development and progression of OSCC. In particular, miR-21 has been implicated in various cellular processes, including proliferation, apoptosis, and invasion; it could be a potential therapeutic target for OSCC. In this study, The Cancer Genome Atlas (TCGA) for OSCC (TCGA-OSCC) clinical information was used. Patient outcomes were analyzed through survival analysis using Kaplan-Meier curves and log-rank tests. The HSC-3cell line was used as the OSCC cell line, which is known for its aggressive characteristics. The expression of Loc646329, miR-21, PTEN, PDCD4, and SPRY2 was evaluated by RT-PCR, flow cytometry, and scratch assay. Also, the effect of Loc646329 expression on OSCC was evaluated using the in vivo Xenograft Mouse Model. The results showed that overexpression of Loc646329 leads to the downregulation of miR-21, PDCD4, and SPRY2 genes while the PTEN gene is upregulated. In other words, the overexpression of Loc646329 by miR-21 inhibition (thorough targeting RAS/MAPK pathway) induces apoptosis and stops the cell cycle in OSCC cells. In vivo tests showed that elevated Loc646329 expression was linked to positive pathological outcomes, such as smaller tumor size, reduced lymph node metastasis, and enhanced overall survival in OSCC patients. In conclusion, the identification of Loc646329 as a sponge for miR-21 and its impact on the RAS/MAPK signaling pathway offers new opportunities for the development of innovative therapeutic strategies for OSCC. Further investigations into this regulatory axis may uncover additional targets for precision medicine approaches in the treatment of OSCC.

摘要

口腔鳞状细胞癌(OSCC)是一种常见且侵袭性强的头颈癌。新出现的证据表明,微小RNA(miRNA)在OSCC的发生和发展中起关键作用。特别是,miR-21已被证明参与多种细胞过程,包括增殖、凋亡和侵袭;它可能是OSCC的一个潜在治疗靶点。在本研究中,使用了OSCC的癌症基因组图谱(TCGA)(TCGA-OSCC)临床信息。通过使用Kaplan-Meier曲线和对数秩检验的生存分析来分析患者的预后。HSC-3细胞系被用作OSCC细胞系,其以侵袭性特征而闻名。通过逆转录-聚合酶链反应(RT-PCR)、流式细胞术和划痕试验评估Loc646329、miR-21、PTEN、PDCD4和SPRY2的表达。此外,使用体内异种移植小鼠模型评估Loc646329表达对OSCC的影响。结果表明,Loc646329的过表达导致miR-21、PDCD4和SPRY2基因的下调,而PTEN基因上调。换句话说,通过miR-21抑制(彻底靶向RAS/丝裂原活化蛋白激酶途径)过表达Loc646329可诱导OSCC细胞凋亡并使细胞周期停滞。体内试验表明,Loc646329表达升高与积极的病理结果相关,如肿瘤尺寸较小、淋巴结转移减少以及OSCC患者总生存期延长。总之,将Loc646329鉴定为miR-21的海绵及其对RAS/丝裂原活化蛋白激酶信号通路的影响为开发OSCC的创新治疗策略提供了新机会。对该调控轴的进一步研究可能会发现OSCC治疗中精准医学方法的其他靶点。

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