Background Increasing evidence has suggested that microRNAs (miRNAs) act as key post-transcriptional regulators in tumor progression. Previous studies have confirmed that miR-17-5p functions as an oncogene in multiple cancers and contributes to tumor progression. However, the role and biological functions of miR-17-5p in the development of laryngeal squamous cell carcinoma (LSCC) still remain unknown. Methods qRT-PCR was used to detect miRNA and mRNA expression levels in LSCC tissues and cell lines. CCK-8 assay was used to measure cell viability and flow cytometry was performed to evaluate cell apoptosis. Western blot analysis was used to detect the protein levels of BAX, BCL-2, cleaved Caspase-3, PIK3R1 and AKT. Luciferase reporter assay was used to detect the effect of miR-17-5p on PIK3R1 expression. Xenograft animal model was used to test the effect of miR-17-5p on LSCC cell in vivo. Results In the present study, we found that miR-17-5p expression level was upregulated in LSCC tissues and cell lines. Depletion of miR-17-5p in LSCC cells significantly reduced cell proliferation and promoted cell apoptosis in vitro and in vivo. Mechanically, knockdown of miR-17-5p in LSCC cells inhibited BCL-2 expression while enhanced BAX and cleaved Caspase-3 protein expression. Moreover, depletion of miR-17-5p in LSCC cells suppressed AKT phosphorylation but did not influence PTEN expression. Importantly, miR-17-5p positively regulated PIK3R1 expression by directly binding to its 3'-untranslated region (UTR). Additionally, PIK3R1, which expression was downregulated in LSCC tissues and cell lines, was involved in LSCC cell survival by modulating the activation of AKT signal pathway. Dysregulation of miR-17-5p/PIK3R1 axis was participated in LSCC cell proliferation and apoptosis by inhibiting the activation of the PI3K/AKT signaling pathway. Conclusions In conclusion, our study indicates that the miR-17-5p/PIK3R1 axis plays an essential role in the development of LSCC and provides a potential therapeutic target for LSCC treatment.

中文翻译：

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miR-17-5p 的沉默通过直接靶向喉鳞状细胞癌中的 PIK3R1 抑制细胞增殖并促进细胞凋亡。

背景 越来越多的证据表明，microRNA (miRNA) 在肿瘤进展中充当关键的转录后调节因子。先前的研究已经证实，miR-17-5p 在多种癌症中作为癌基因发挥作用，并有助于肿瘤进展。然而，miR-17-5p在喉鳞状细胞癌（LSCC）发展中的作用和生物学功能仍然未知。方法 qRT-PCR 检测 LSCC 组织和细胞系中 miRNA 和 mRNA 的表达水平。CCK-8测定用于测量细胞活力并进行流式细胞术以评估细胞凋亡。Western印迹分析用于检测BAX、BCL-2、cleaved Caspase-3、PIK3R1和AKT的蛋白水平。荧光素酶报告基因检测用于检测 miR-17-5p 对 PIK3R1 表达的影响。采用异种移植动物模型检测miR-17-5p在体内对LSCC细胞的影响。结果 在本研究中，我们发现 miR-17-5p 在 LSCC 组织和细胞系中的表达水平上调。在体外和体内，LSCC 细胞中 miR-17-5p 的消耗显着降低了细胞增殖并促进了细胞凋亡。机械地，在 LSCC 细胞中敲低 miR-17-5p 会抑制 BCL-2 表达，同时增强 BAX 并切割 Caspase-3 蛋白表达。此外，LSCC 细胞中 miR-17-5p 的消耗抑制了 AKT 磷酸化，但不影响 PTEN 表达。重要的是，miR-17-5p 通过直接结合 PIK3R1 的 3'-非翻译区 (UTR) 正向调节 PIK3R1 的表达。此外，在 LSCC 组织和细胞系中表达下调的 PIK3R1，通过调节 AKT 信号通路的激活参与 LSCC 细胞的存活。miR-17-5p/PIK3R1轴的失调通过抑制PI3K/AKT信号通路的激活参与了LSCC细胞的增殖和凋亡。结论 总之，我们的研究表明 miR-17-5p/PIK3R1 轴在 LSCC 的发展中起重要作用，并为 LSCC 的治疗提供了潜在的治疗靶点。