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通过综合生物信息学和体外分析探索MiR-484调控:一种在宫颈癌中有前景的生物标志物和治疗靶点

Exploring MiR-484 Regulation by : A Promising Biomarker and Therapeutic Target in Cervical Cancer through Integrated Bioinformatics and an In Vitro Analysis.

作者信息

Niu Jiaojiao, Chen Yeng, Chai Hwa Chia, Sasidharan Sreenivasan

机构信息

Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, Malaysia.

School of Biological Engineering, Xinxiang University, Xinxiang 453003, China.

出版信息

Biomedicines. 2024 Apr 19;12(4):909. doi: 10.3390/biomedicines12040909.

Abstract

BACKGROUND

MiR-484, implicated in various carcinomas, holds promise as a prognostic marker, yet its relevance to cervical cancer (CC) remains unclear. Our prior study demonstrated the downregulation of miR-484, inhibiting HeLa cells. This study investigates miR-484's potential as a biomarker and therapeutic target in CC through integrated bioinformatics and an in vitro analysis.

METHODS

MiR-484 levels were analyzed across cancers, including CC, from The Cancer Genome Atlas. The limma R package identified differentially expressed genes (DEGs) between high- and low-miR-484 CC cohorts. We assessed biological functions, tumor microenvironment (TME), immunotherapy, stemness, hypoxia, RNA methylation, and chemosensitivity differences. Prognostic genes relevant to miR-484 were identified through Cox regression and Kaplan-Meier analyses, and a prognostic model was captured via multivariate Cox regression. Single-cell RNA sequencing determined cell populations related to prognostic genes. qRT-PCR validated key genes, and the miR-484 effect on CC proliferation was assessed via an MTT assay.

RESULTS

MiR-484 was upregulated in most tumors, including CC, with DEGs enriched in skin development, PI3K signaling, and immune processes. High miR-484 expression correlated with specific immune cell infiltration, hypoxia, and drug sensitivity. Prognostic genes identified were predominantly epidermal and stratified patients with CC into risk groups, with the low-risk group showing enhanced survival and immunotherapeutic responses. qRT-PCR confirmed FGFR3 upregulation in CC cells, and an miR-484 mimic reversed the inhibitory effect on HeLa proliferation.

CONCLUSION

MiR-484 plays a crucial role in the CC progression and prognosis, suggesting its potential as a biomarker for targeted therapy.

摘要

背景

MiR - 484与多种癌症相关,有望成为一种预后标志物,但其与宫颈癌(CC)的相关性仍不明确。我们之前的研究表明MiR - 484下调可抑制HeLa细胞。本研究通过综合生物信息学和体外分析,探讨MiR - 484作为CC生物标志物和治疗靶点的潜力。

方法

分析来自癌症基因组图谱中包括CC在内的多种癌症的MiR - 484水平。使用limma R包鉴定高、低MiR - 484 CC队列之间的差异表达基因(DEG)。我们评估了生物学功能、肿瘤微环境(TME)、免疫治疗、干性、缺氧、RNA甲基化和化疗敏感性差异。通过Cox回归和Kaplan - Meier分析确定与MiR - 484相关的预后基因,并通过多变量Cox回归建立预后模型。单细胞RNA测序确定与预后基因相关的细胞群体。qRT - PCR验证关键基因,并通过MTT试验评估MiR - 484对CC增殖的影响。

结果

MiR - 484在包括CC在内的大多数肿瘤中上调,DEG在皮肤发育、PI3K信号传导和免疫过程中富集。高MiR - 484表达与特定免疫细胞浸润、缺氧和药物敏感性相关。鉴定出的预后基因主要为表皮和分层相关基因,可将CC患者分为风险组,低风险组显示出更高的生存率和免疫治疗反应。qRT - PCR证实CC细胞中FGFR3上调,MiR - 484模拟物可逆转对HeLa增殖的抑制作用。

结论

MiR - 484在CC进展和预后中起关键作用,表明其作为靶向治疗生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9167/11047986/0c32e34965ba/biomedicines-12-00909-g001.jpg

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