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微小RNA-493-5p通过靶向缺氧诱导因子-1α在头颈部鳞状细胞癌进展中发挥肿瘤抑制作用。

MiR-493-5p functions as a tumour suppressor in head and neck squamous cell carcinoma progression by targeting HIF-1α.

作者信息

Liu Jiahui, Tian Ruxian, Chen Xi, Song Qing, Sun Caiyu, Li Dongxian, Fang Yuhui, Lv Shijun, Li Yumei, Song Xicheng

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, 264000, China.

Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, China.

出版信息

Discov Oncol. 2025 May 24;16(1):899. doi: 10.1007/s12672-025-02690-1.

Abstract

BACKGROUND

Head and neck squamous cell carcinoma (HNSCC) demonstrates insidious onset, high prevalence, and low 5-year overall survival rate. While downregulation of miR-493-5p is implicated in the development of various cancers, its role in HNSCC remains unclear. Here, we explored the association of miR-493-5p with HNSCC progression and elucidated the underlying mechanisms.

METHODS

The miR-493-5p expression in HNSCC tissues and cells was verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation and migration were detected by Cell Counting Kit 8, colony formation, and wound-healing assay. Dual-luciferase reporter gene assay was used to verify that miR-493-5p targeted hypoxia-inducible factor (HIF)-1α. Cobalt chloride (CoCl) was used to induce HIF-1α expression to perform rescue assays. SCC VII cells were used to construct the mouse model. After 15 days, the tumour volume was compared. The expression of HIF-1α, glycolysis, and epithelial-mesenchymal transition (EMT) proteins were verified by western blotting.

RESULTS

MiR-493-5p expression was low and beneficial to prognosis in HNSCC tumours. MiR-493-5p constrained HNSCC cell proliferation and migration and inhibited HIF-1α expression by targeting its 3' untranslated region directly. CoCl addition reduced miR-493-5p-induced cell proliferation, which may be related to the increased expression of HIF-1α. MiR-493-5p decelerated tumour cell growth in mice and was associated with glycolysis and EMT in HNSCC cells.

CONCLUSIONS

MiR-493-5p, which targets HIF-1α and inhibits glycolysis and EMT, may be a novel therapeutic target for HNSCC.

摘要

背景

头颈部鳞状细胞癌(HNSCC)起病隐匿,患病率高,5年总生存率低。虽然miR-493-5p的下调与多种癌症的发生发展有关,但其在HNSCC中的作用仍不清楚。在此,我们探讨了miR-493-5p与HNSCC进展的关系,并阐明了其潜在机制。

方法

通过定量逆转录聚合酶链反应(qRT-PCR)验证HNSCC组织和细胞中miR-493-5p的表达。采用细胞计数试剂盒8、集落形成和伤口愈合试验检测细胞增殖和迁移。双荧光素酶报告基因试验用于验证miR-493-5p靶向缺氧诱导因子(HIF)-1α。用氯化钴(CoCl)诱导HIF-1α表达以进行挽救试验。用SCC VII细胞构建小鼠模型。15天后,比较肿瘤体积。通过蛋白质免疫印迹法验证HIF-1α、糖酵解和上皮-间质转化(EMT)蛋白的表达。

结果

miR-493-5p在HNSCC肿瘤中的表达较低,对预后有益。miR-493-5p通过直接靶向其3'非翻译区抑制HNSCC细胞增殖和迁移,并抑制HIF-1α表达。添加CoCl可降低miR-493-5p诱导的细胞增殖,这可能与HIF-1α表达增加有关。miR-493-5p减缓了小鼠肿瘤细胞的生长,并与HNSCC细胞中的糖酵解和EMT有关。

结论

靶向HIF-1α并抑制糖酵解和EMT的miR-493-5p可能是HNSCC的一个新的治疗靶点。

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