miR-19a mediates the mechanism by which SPHK2 regulates hypopharyngeal squamous cell carcinoma progression through the PI3K/AKT axis.
miR-19a mediates the mechanism by which SPHK2 regulates hypopharyngeal squamous cell carcinoma progression through the PI3K/AKT axis.
复制标题
miR-19a 介导 SPHK2 通过 PI3K/AKT 轴调节下咽鳞状细胞癌进展的机制。
DOI：
--
复制
发表时间：
2023
影响因子：
5.3
通讯作者：
G. Hu
中科院分区：
文献类型：
--
作者：
Ji Song;Yanshi Li;T. Lu;Min Pan;Zhihai Wang;Chuan Liu;Y. Liao;G. Hu
本研究旨在探讨下咽鳞状细胞癌（Hypopharyngeal squamous cell carcinoma，HSCC）患者中鞘氨醇激酶2（sphingosine kinase 2，SPHK 2）和microRNA miR-19 a-3 p（miR-19 a-3 p）的表达及其对HSCC侵袭和转移的影响。采用实时定量PCR和Western blotting方法检测SPHK 2和miR-19 a-3 p在HSCC淋巴结转移（LNM）患者中的表达。将免疫组化（IHC）结果与临床信息一起分析，以评估其临床意义。随后，在体外实验中评估SPHK 2过表达和敲低对FaDu细胞的功能影响。我们使用裸鼠进行体内实验以评估SPHK 2敲低对肿瘤形成、生长和LNM的影响。最后，我们探讨了SPHK 2在HSCC中的上游和下游信号通路。SPHK 2在伴淋巴结转移的HSCC患者中表达显著升高，SPHK 2表达增强的患者生存率较低（P < 0.05）。我们还证明SPHK 2过表达加速了增殖、迁移和侵袭。使用动物模型，我们进一步验证了SPHK 2缺失消除了肿瘤生长和LNM。在机制方面，我们发现miR-19 a-3 p在伴有LNM的HSCC患者中显著降低，并且与SPHK 2呈负相关。miR-19 a-3 p和SPHK 2可通过PI 3 K/AKT轴调节肿瘤的增殖和侵袭。SPHK 2被发现对LNM和HSCC患者的预后有显著贡献，并且被证明是LNM和HSCC患者分期的独立风险因素。发现miR-19 a-3 p/SPHK 2/PI 3 K/AKT轴有助于HSCC的发展和结果。
This study explored the expression of sphingosine kinase 2 (SPHK2) and microRNA miR-19a-3p (miR-19a-3p) in patients with Hypopharyngeal squamous cell carcinoma (HSCC) together with pathways affecting HSCC invasion and metastasis. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) were performed to assess the differential expression of SPHK2 and miR-19a-3p in patients with HSCC lymph node metastasis (LNM). Immunohistochemical (IHC) results were analyzed together with clinical information to evaluate their clinical significance. Subsequently, the functional effects of SPHK2 overexpression and knockdown on FaDu cells were evaluated in in vitro experiments. We performed in vivo experiments using nude mouse to assess the effects of SPHK2 knockdown on tumor formation, growth and LNM. Finally, we explored upstream and downstream signaling pathways associated with SPHK2 in HSCC. SPHK2 was significantly elevated in HSCC patients with LNM and survival was lower in patients with enhanced SPHK2 expression (P < 0.05). We also demonstrated that SPHK2 overexpression accelerated the proliferation, migration, and invasion. Using animal models, we further verified that SPHK2 deletion abrogated tumor growth and LNM. In terms of mechanism, we found that miR-19a-3p was significantly reduced in HSCC patients with LNM and was negatively associated with SPHK2. MiR-19a-3p and SPHK2 could regulate tumor proliferation and invasion through the PI3K/AKT axis. SPHK2 was found to contribute significantly to both LNM and HSCC patient prognosis and was shown to be an independent risk factor for LNM and staging in HSCC patients. The miR-19a-3p/SPHK2/PI3K/AKT axis was found to contribute to the development and outcome of HSCC.