SEC14L1P1对口腔鳞状细胞癌细胞增殖和迁移的影响
Effects of SEC14L1P1 on proliferation and migration of oral squamous cell carcinoma cells
摘要
Abstract
Background and purpose:SEC14L1P1,a pseudogene of the SEC14 family,is closely associated with the development of various tumors,but its role in oral squamous cell carcinoma(OSCC)has not been clarified.This study aimed to gain insights into the expression characteristics and subcellular localization of SEC14L1P1 in OSCC cells,as well as its effects on OSCC cell proliferation and migration.Methods:The expression of SEC14L1P1 in head and neck squamous cell carcinoma(HNSCC)tissues was analyzed by the ENCORI database;The expression of SEC14L1P1 and its relationship with patient prognosis in HNSCC was further analyzed using the GDC and UCSC Xena databases.The expression of SEC14L1P1 in OSCC cell lines was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR);RNA nucleoplasmic separation assay was performed to determine the localization of SEC14L1P1 in OSCC cells.SEC14L1P1 knockdown(SS-SEC14L1P1)group and knockdown control(SS-NC)group were established for CAL-27 cells,and SEC14L1P1 overexpression(SEC14L1P1)group and overexpression control(Vector)group were established for HN30 cells.The effects of SEC14L1P1 expression on the proliferation and migration abilities of cells in each group were assessed by cell counting kit-8(CCK-8)and transwell migration assays.RTFQ-PCR and Western blot experiments were used to detect the effects of altered SEC14L1P1 expression on the expression levels of epithelial-mesenchymal transition(EMT)-related genes.To investigate the effects of SEC14L1P1 on the proliferation of OSCC cells in vivo using a subcutaneous xenograft tumor model in nude mice,12 four-week-old BALB/c nude mice were randomly divided into two groups:the antisense oligonucleotide(ASO)-NC group and the ASO-SEC14L1P1 group,with 6 mice in each group.All mice were individually labeled.Further mechanistic studies were performed by analyzing molecules interacting with SEC14L1P1 through the RNAInter database,and the ENCORI database was queried for expression correlation between SEC14L1P1 and DHX9.The effect of altered SEC14L1P1 expression on the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway was detected by Western blot assay.Results:Database analysis showed that the expression of SEC14L1P1 was higher in HNSCC tissues than in normal tissues,and was strongly associated with poor patient prognosis.The RTFQ-PCR results showed that SEC14L1P1 was highly expressed in all six OSCC cell lines;RNA nucleoplasmic separation showed that SEC14L1P1 was mainly localized in the nucleus in CAL-27 and HN30 cells.Compared with SS-NC,the relative expression of SEC14L1P1 in the SS-SEC14L1P1 group was significantly lower and significantly inhibited cell proliferation and migration,while the relative expression of SEC14L1P1 in the SEC14L1P1 group was significantly higher compared with the Vector group,which also significantly increased cell proliferation and migration.The down-regulation of SEC14L1P1 was accompanied by increased mRNA and protein levels of E-cadherin,and decreased mRNA and protein levels of N-cadherin and vimentin,with the opposite result after SEC14L1P1 overexpression.In vivo experiments showed that the xenograft tumor weight and volume of the ASO-SEC14L1P1 group were significantly reduced.Further mechanistic studies revealed a positive correlation between SEC14L1P1 and DHX9 expressions,and DHX9 has been shown to activate the PI3K/AKT signaling pathway.Knockdown of SEC14L1P1 resulted in decreased protein expressions of phosphorylated-PI3K(p-PI3K)and phosphorylated-AKT(p-AKT),and overexpression of SEC14L1P1 increased protein expressions of p-PI3K and p-AKT.Conclusion:SEC14L1P1 showed high expression levels in OSCC cells and tissues and promoted the proliferation and migration of OSCC cells,a phenomenon that may be related to the regulation of the PI3K/AKT signaling pathway by SEC14L1P1,which in turn promotes EMT.关键词
SEC14L1P1/口腔鳞状细胞癌/细胞增殖/细胞迁移/上皮-间充质转化Key words
SEC14L1P1/Oral squamous cell carcinoma/Cell proliferation/Cell migration/Epithelial-mesenchymal transition分类
医药卫生引用本文复制引用
郑文甜,公慧,张馨月,郝嘉仪,王亚杰,蒋英英..SEC14L1P1对口腔鳞状细胞癌细胞增殖和迁移的影响[J].中国癌症杂志,2025,35(3):309-319,11.基金项目
山东省自然科学基金资助项目(ZR2023LSW019) (ZR2023LSW019)
2021年山东省高等学校"青创人才引育计划"支持项目(2021-5) (2021-5)
山东第二医科大学研究生科研创新基金(2023YJSCX005,2024YJSCX004) (2023YJSCX005,2024YJSCX004)
山东省大学生创新创业训练计划项目(S202410438019) (S202410438019)
2022年度山东省教育系统政府公派出国留学项目"省校联合培养计划"(2022-80). Shandong Provincial Natural Science Foundation(ZR2023LSW019) (2022-80)
2021 Youth Innovation Talent Introduction and Education Program of Shandong Province Universities(2021-5) (2021-5)
Graduate Student Research Grant from Shandong Second Medical University(2023YJSCX005,2024YJSCX004) (2023YJSCX005,2024YJSCX004)
Shandong Provincial College Students'Innovation and Entrepreneurship Training Program(S202410438019) (S202410438019)
Shandong Provincial Government sponsored"Provincial-University Joint Training Program"for studying abroad(2022-80).Conflicts of interest:no. (2022-80)