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

Author:

Niu Jiaojiao12,Chen Yeng3,Chai Hwa Chia4ORCID,Sasidharan Sreenivasan1

Affiliation:

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

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

3. Department of Oral & Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur 50603, Malaysia

4. Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia

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 Polyalthia longifolia 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 P. longifolia 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.

Publisher

MDPI AG

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