miR-19a mediates the mechanism by which SPHK2 regulates hypopharyngeal squamous cell carcinoma progression through the PI3K/AKT axis

作者全名："Song, Ji; Li, Yanshi; Lu, Tao; Pan, Min; Wang, Zhihai; Liu, Chuan; Liao, Yang; Hu, Guohua"

作者地址："[Song, Ji; Liao, Yang] Chongqing Med Univ, Univ Town Hosp, Dept Otorhinolaryngol, Chongqing, Peoples R China; [Song, Ji; Li, Yanshi; Lu, Tao; Pan, Min; Wang, Zhihai; Liu, Chuan; Hu, Guohua] Chongqing Med Univ, Affiliated Hosp 1, Dept Otorhinolaryngol, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Hu, GH (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Otorhinolaryngol, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：AMERICAN JOURNAL OF CANCER RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001024486600008

JCR分区：Q2

影响因子：3.6

年份：2023

卷号：13

期号：6

开始页：2342

结束页：2359

文献类型：Article

关键词：SPHK2; hypopharyngeal squamous cell carcinoma; lymph node metastasis; miRNA-19a-3p; PI3P; AKT; pathway

摘要："This study explored the expression of sphingosine kinase 2 (SPHK2) and microRNA miR-19a-3p (miR19a-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."

基金机构："Center for Molecular Medicine and Cancer Research of Chongqing Medical University; National Natural Science Foundation of China [82173303]; Natural Science Foundation of Chongqing, China [cstc2021ycjh-bgzxm0149]; National Natural Science Foundation of Chongqing [Cstc2020jcyj-msxmX1098]; Humanities and Social Sciences Research program of Chongqing Municipal Education Commission [22SKGH-073]; Scientific Research Funding of University-Town Hospital of Chongqing Medical University [2021JC04]"

基金资助正文："We would like to thank the Center for Molecular Medicine and Cancer Research of Chongqing Medical University for providing experimental equipment and an experimental platform. Thanks for the technical support from the Department of Pathology, the First Affiliated Hospital of Chongqing Medical University. This study was supported by National Natural Science Foundation of China (Grant No. 82173303) , Natural Science Foundation of Chongqing, China (Grant No. cstc2021ycjh-bgzxm0149) , National Natural Science Foundation of Chongqing (Grant No. Cstc2020jcyj-msxmX1098) , Humanities and Social Sciences Research program of Chongqing Municipal Education Commission (Grant No. 22SKGH-073) and Scientific Research Funding of University-Town Hospital of Chongqing Medical University (account number 2021JC04) ."