LncRNA PGM5-AS1通过调控Hippo和PI3K-AKT通路影响宫颈癌对顺铂的耐药性

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2024-12-28 DOI:10.1007/s10528-024-11011-0
Huimin Wang, Yi Yang, Enjing Zhang, Dan Wang, Weiqiong Cai, Chun Li, Qiong Wei
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引用次数: 0

摘要

顺铂是一种以铂为基础的化疗药物,可用于宫颈癌(CC)的治疗,但顺铂治疗过程中顺铂耐药性增加。据报道,长链非编码RNA PGM5-AS1参与CC肿瘤发生;然而,其在顺铂耐药CC患者中的作用尚未揭示。本研究旨在探讨PGM5-AS1在调节CC顺铂耐药中的作用,采用定量逆转录-聚合酶链反应对29例CC患者组织中PGM5-AS1的表达进行定量分析。通过增加顺铂浓度构建顺铂耐药CC细胞。通过细胞计数试剂盒8、菌落形成、伤口愈合和transwell试验证实顺铂耐药与PGM5-AS1相互作用对CC细胞恶性肿瘤的影响。Western blotting检测Hippo和PI3K-AKT信号通路的关键蛋白。PGM5-AS1在CC组织中低表达与国际妇产联合会分期高、分化差、淋巴结转移、顺铂耐药相关。PGM5-AS1过表达抑制顺铂耐药CC细胞的增殖、迁移和侵袭能力。此外,PGM5-AS1在顺铂耐药CC细胞中的过表达可诱导Hippo信号通路的激活和PI3K-AKT信号通路的失活。PGM5-AS1通过激活Hippo信号通路和灭活PI3K-AKT信号通路增强CC细胞对顺铂的敏感性。我们的研究数据可能为CC治疗中克服顺铂耐药提供一种新的治疗性生物标志物。
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LncRNA PGM5-AS1 Impairs the Resistance of Cervical Cancer to Cisplatin by Regulating the Hippo and PI3K-AKT Pathways.

Cisplatin, a platinum-based chemotherapeutic agent, can be used to treat cervical cancer (CC), but cisplatin resistance is increased during the cisplatin treatment. Long non-coding RNA PGM5-AS1 reportedly participates in CC tumorigenesis; however, its role in CC patients with cisplatin resistance has not been revealed. The present aimed to examine the role of PGM5-AS1 in modulating cisplatin resistance in CC. The PGM5-AS1 expression in CC tissues from 29 patients was quantified using quantitative reverse transcription-polymerase chain reaction. The cisplatin-resistant CC cells were constructed by using increasing cisplatin concentrations. The effects of cisplatin resistance interacting with PGM5-AS1 on CC cell malignancy were confirmed by performing Cell Counting Kit 8, colony formation, wound healing, and transwell assays. The key proteins of the Hippo and PI3K-AKT signaling pathways were evaluated by Western blotting. PGM5-AS1 with low expression in CC tissues was correlated to higher International Federation of Gynecology and Obstetrics stage, poor differentiation, lymph node metastasis, and cisplatin resistance. PGM5-AS1 overexpression suppressed the proliferation, migration, and invasion abilities of cisplatin-resistant CC cells. Additionally, PGM5-AS1 overexpression in cisplatin-resistant CC cells could induce the activation of the Hippo signaling pathway and the inactivation of the PI3K-AKT signaling pathway. PGM5-AS1 enhanced the CC cell's sensitivity to cisplatin by activating the Hippo signaling pathway and inactivating the PI3K-AKT signaling pathway. Our study data may provide a novel therapeutic biomarker to overcome cisplatin resistance in CC treatment.

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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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