由GAS5/miR-3127-5p调控的PRELP抑制口腔鳞状细胞癌中的顺铂耐药性。
PRELP regulated by GAS5/miR-3127-5p suppresses cisplatin resistance in oral squamous cell carcinoma.
作者信息
Sun Xiaoni, Liu Yang, Chai Luyi, Zhou Jianbo
机构信息
Department of Stomatology, The Affiliated People's Hospital of Ningbo University, No. 251, Baizhang East Road, Yinzhou District, Ningbo, 315040 Zhejiang Province China.
出版信息
Cytotechnology. 2025 Jun;77(3):92. doi: 10.1007/s10616-025-00749-z. Epub 2025 Apr 28.
UNLABELLED
Our previous study has identified that PRELP inhibits the progression of oral squamous cell carcinoma (OSCC). This study aimed to investigate the influence of PRELP on cisplatin (DDP) resistance in OSCC cells and to elucidate the underlying mechanism. The levels of PRELP, miR-3127-5p, and GAS5 in established DDP-resistant OSCC cell lines (CAL27/DDP and SCC-15/DDP) and parental cells were detected. Following transfection with PRELP overexpressing or silencing plasmids in DDP-resistant OSCC cells, DDP resistance was evaluated by the IC50 values, proliferation, apoptosis and ABCB1 expression. Bioinformatic analysis, dual-luciferase reporter assays, and rescue experiments were employed to explore the upstream miRNA and lncRNA of PRELP. Our results demonstrated that in both DDP-resistant cells, PRELP and GAS5 levels were decreased, while miR-3127-5p expression was increased compared with parental cells. PRELP overexpression reduced the IC50 of DDP and EdU-positive cell number, enhanced cell apoptosis, and suppressed ABCB1 expression in resistant cells. Conversely, PRELP silencing caused opposite effects. In the TCGA database, miR-3127-5p was highly expressed in HNSC, and patients with higher miR-3127-5p expression had shorter overall survival. A negative correlation was observed between miR-3127-5p and PRELP in HNSC. miR-3127-5p promoted DDP resistance in OSCC by targeting PRELP. GAS5 positively modulated PRELP expression by sponging miR-3127-5p. The alleviation of DDP resistance by GAS5 was attenuated by miR-3127-5p mimic and PRELP downregulation. In conclusion, PRELP, which is regulated by lncRNA GAS5/miR-3127-5p axis, suppresses DDP resistance in OSCC through decreasing ABCB1 expression. Targeting the GAS5/miR-3127-5p/PRELP axis may offer a promising strategy to overcome DDP resistance in OSCC.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s10616-025-00749-z.
未标注
我们之前的研究已确定脯氨酸丰富的细胞外基质蛋白（PRELP）可抑制口腔鳞状细胞癌（OSCC）的进展。本研究旨在探讨PRELP对OSCC细胞顺铂（DDP）耐药性的影响，并阐明其潜在机制。检测了已建立的DDP耐药OSCC细胞系（CAL27/DDP和SCC-15/DDP）及亲代细胞中PRELP、miR-3127-5p和生长停滞特异性转录本5（GAS5）的水平。在用PRELP过表达或沉默质粒转染DDP耐药OSCC细胞后，通过半数抑制浓度（IC50）值、增殖、凋亡和ATP结合盒转运蛋白B1（ABCB1）表达来评估DDP耐药性。采用生物信息学分析、双荧光素酶报告基因检测和拯救实验来探究PRELP的上游微小RNA（miRNA）和长链非编码RNA（lncRNA）。我们的结果表明，与亲代细胞相比，在两种DDP耐药细胞中，PRELP和GAS5水平均降低，而miR-3127-5p表达增加。PRELP过表达降低了DDP的IC50和5-乙炔基-2'-脱氧尿苷（EdU）阳性细胞数，增强了细胞凋亡，并抑制了耐药细胞中ABCB1的表达。相反，PRELP沉默则产生相反的效果。在癌症基因组图谱（TCGA）数据库中，miR-3127-5p在头颈部鳞状细胞癌（HNSC）中高表达，miR-3127-5p表达较高的患者总生存期较短。在HNSC中观察到miR-3127-5p与PRELP呈负相关。miR-3127-5p通过靶向PRELP促进OSCC中的DDP耐药性。GAS5通过海绵吸附miR-3127-5p正向调节PRELP表达。miR-3127-5p模拟物和PRELP下调减弱了GAS5对DDP耐药性的缓解作用。总之，由lncRNA GAS5/miR-3127-5p轴调控的PRELP通过降低ABCB1表达抑制OSCC中的DDP耐药性。靶向GAS5/miR-3127-5p/PRELP轴可能为克服OSCC中的DDP耐药性提供一种有前景的策略。
补充信息
在线版本包含可在10.1007/s10616-025-00749-z获取的补充材料。
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