PRELP regulated by GAS5/miR-3127-5p suppresses cisplatin resistance in oral squamous cell carcinoma.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2025-06-01 Epub Date: 2025-04-28 DOI:10.1007/s10616-025-00749-z

Xiaoni Sun, Yang Liu, Luyi Chai, Jianbo Zhou

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引用次数: 0

Abstract

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.

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GAS5/miR-3127-5p调控的PRELP抑制口腔鳞状细胞癌顺铂耐药

我们之前的研究已经发现，PRELP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）耐药的影响并阐明其机制。检测已建立的耐药OSCC细胞系（CAL27/DDP和SCC-15/DDP）和亲本细胞中PRELP、miR-3127-5p和GAS5的水平。在耐DDP的OSCC细胞中转染过表达或沉默的PRELP质粒后，通过IC50值、增殖、凋亡和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、救援实验等方法对PRELP上游miRNA和lncRNA进行研究。我们的研究结果表明，与亲本细胞相比，在两种ddp耐药细胞中，PRELP和GAS5水平均降低，而miR-3127-5p表达升高。PRELP过表达降低耐药细胞DDP和edu阳性细胞的IC50，增强细胞凋亡，抑制ABCB1的表达。相反，沉默PRELP会产生相反的效果。在TCGA数据库中，miR-3127-5p在HNSC中高表达，miR-3127-5p高表达的患者总生存期较短。HNSC中miR-3127-5p与PRELP呈负相关。miR-3127-5p通过靶向PRELP促进OSCC对DDP的抗性。GAS5通过海绵miR-3127-5p正向调节PRELP的表达。通过miR-3127-5p模拟物和PRELP下调，GAS5对DDP抗性的缓解被减弱。综上所述，受lncRNA GAS5/miR-3127-5p轴调控的PRELP通过降低ABCB1的表达抑制OSCC对DDP的抗性。靶向GAS5/miR-3127-5p/PRELP轴可能是克服OSCC中DDP耐药的一种有希望的策略。补充信息：在线版本包含补充资料，可在10.1007/s10616-025-00749-z获得。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.