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Effects of
SEC14L1P1 on proliferation and migration of oral squamous cell carcinoma cells- China Oncology Vol. 35, Issue 3, Pages: 309-319(2025)
- 作者机构：
山东第二医科大学口腔医学院，山东 潍坊 261053
- 作者简介：
- 基金信息：Shandong Provincial Natural Science Foundation(ZR2023LSW019);2021 Youth Innovation Talent Introduction and Education Program of Shandong Province Universities(2021-5);Graduate Student Research Grant from Shandong Second Medical University(2023YJSCX005);Graduate Student Research Grant from Shandong Second Medical University(2024YJSCX004);Shandong Provincial College Students’ Innovation and Entrepreneurship Training Program(S202410438019);Shandong Provincial Government sponsored “Provincial-University Joint Training Program” for studying abroad(2022-80)
DOI：10.19401/j.cnki.1007-3639.2025.03.007
CLC： R739.85Received：30 July 2024，
Revised：2025-02-06，
Published：30 March 2025
- 稿件说明：
移动端阅览
Wentian ZHENG, Hui GONG, Xinyue ZHANG, et al. Effects of
SEC14L1P1 on proliferation and migration of oral squamous cell carcinoma cells[J]. China Oncology, 2025, 35(3): 309-319.Wentian ZHENG, Hui GONG, Xinyue ZHANG, et al. Effects of
SEC14L1P1 on proliferation and migration of oral squamous cell carcinoma cells[J]. China Oncology, 2025, 35(3): 309-319. DOI： 10.19401/j.cnki.1007-3639.2025.03.007.
摘要
背景与目的：
SEC14L1P1
是SEC14家族的一种假基因
已被发现与多种肿瘤的发生、发展密切相关
但其在口腔鳞状细胞癌（oral squamous cell carcinoma
OSCC）中的作用尚未明确。本研究旨在深入了解
SEC14L1P1
在OSCC细胞内的表达特征和
亚细胞定位
以及其对OSCC细胞增殖和迁移的影响。
方法：
通过ENCORI数据库对
SEC14L1P1
在头颈部鳞状细胞癌（head and neck squamous cell carcinoma
HNSCC）组织中的表达进行分析；利用GDC和UCSC Xena数据库进一步分析
SEC14L1P1
在HNSCC中的表达及其与患者预后之间的关系。利用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction
RTFQ-PCR）检测
SEC14L1P1
在OSCC细胞系中的表达；采用RNA核质分离实验确定
SEC14L1P1
在OSCC细胞中的定位。对CAL-27细胞建立
SEC14L1P1
敲减（SS-
SEC14L1P1
）组和敲减对照（SS-NC）组
对HN30细胞建立
SEC14L1P1
过表达（SEC14L1P1）组和过表达对照（Vector）组。通过细胞计数试剂盒-8（cell counting kit-8
CCK-8）和transwell迁移实验评估
SEC14L1P1
表达变化对各组细胞增殖、迁移能力的影响。采用RTFQ-PCR和蛋白质印迹法（Western blot）检测
SEC14L1P1
表达改变对上皮-间充质转化（epithelial-mesenchymal transition
EMT）相关基因表达水平的影响。采用裸鼠皮下移植瘤模型观察
SEC14L1P1
在体内对OSCC细胞增殖的影响
将12只4周龄BALB/c裸鼠随机分为反义寡核苷酸（antisense oligonucleotide
ASO）-NC组和ASO-
SEC14L1P1
组
每组6只
每只裸鼠均做标记。进一步的机制研究通过RNAInter数据库分析与
SEC14L1P1
交互的分子
通过ENCORI数据库查询
SEC14L1P1
与DHX9的表达相关性。采用Western blot检测
SEC14L1P1
表达改变对磷脂酰肌醇3-激酶（phosphoinositide 3-kinase
PI3K）/蛋白激酶B（protein kinase B
AKT）通路的影响。
结果：
数据库分析显示
SEC14L1P1
在HNSCC组织中的表达高于正常组织
且与患者的不良预后密切相关。RTFQ-PCR结果表明
SEC14L1P1
在6种OSCC细胞系中均高表达；RNA核质分离实验结果显示
在CAL-27和HN30细胞中
SEC14L1P1
主要定位于细胞核内。与SS-NC组相比
SS-SEC14L1P1组中的相对表达水平明显降低
且能显著抑制细胞增殖和迁移能力；与Vector组相比
SEC14L1P1
组中的相对表达水平明显升高
细胞增殖和迁移能力也明显升高。
SEC14L1P1
的下调伴随E-钙粘蛋白（E-cadherin）的mRNA表达和蛋白水平升高
N-钙粘蛋白（N-cadherin）和波形蛋白（vimentin）的mRNA表达和蛋白水平降低
SEC14L1P1
过表达后的结果则相反。裸鼠皮下移植瘤模型实验显示
与ASO-NC组比较
ASO-
SEC14L1P1
组皮下移植瘤体积和重量均减小。进一步的机制研究发现
SEC14L1P1
与DHX9表达呈正相关性
且已有研究表明DHX9能激活PI3K/AKT信号通路；敲减
SEC14L1P1
导致磷酸化PI3K（phosphorylated-PI3K
p-PI3K）和磷酸化AKT（phosphorylated-AKT
p-AKT）的蛋白表达减少
过表达
SEC14L1P1
则显示p-PI3K和p-AKT的蛋白表达增加。
结论：
SEC14L1P1
在OSCC细胞和组织中呈现出较高的表达水平
并且能促进OSCC细胞增殖及迁移
这一现象可能与
SEC14L1P1
调控PI3K/AKT信号通路
进而促进EMT有关。
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 g
roups: 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 expressio
ns 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
Keywords
references
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