ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1642999
This article is part of the Research TopicInnovations in Biomarker-Based Lung Cancer ScreeningView all 14 articles
MiR-4664-3p as a Potential Diagnostic, Prognostic, and Immunotherapeutic Biomarker in NSCLC: Modulation of Tumor Progression through CD8 + T Cell Regulation
Provisionally accepted
- 1Medical School, Hunan University of Chinese Medicine, Changsha, China
- 2School of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
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Introduction: Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide, largely due to complex interactions within the tumor-immune microenvironment that limit treatment efficacy. MicroRNAs (miRNAs) play critical roles in the regulation of tumor progression and immune evasion. This study systematically evaluated the expression characteristics, clinical significance, and role of miR-4664-3p in tumor immune regulation in NSCLC. Methods: We analyzed an NSCLC dataset from The Cancer Genome Atlas (TCGA) and identified miR-4664-3p as a potential diagnostic, prognostic, and immunotherapeutic biomarker. Bioinformatic approaches have been used to assess miRNA expression and clinical significance. The regulatory role of the miR-4664-3p/Protein Kinase C Beta (PRKCB) axis was further examined using correlation analysis, nomogram construction, and experimental validation in cell lines and animal models. Results: MiR-4664-3p was significantly upregulated in NSCLC tissues and served as an independent predictor of poor prognosis. Its increased expression was linked to reduced immune cell infiltration and enhanced immune escape. PRKCB was validated as a direct downstream target of miR-4664-3p and showed a positive association with CD8 + T cell infiltration and favorable outcomes. Functional assays confirmed that miR-4664-3p promoted NSCLC cell proliferation, migration, and invasion. Conversely, the inhibition of miR-4664-3p increased PRKCB expression, boosted CD8 + T cell activity, strengthened anti-tumor immunity, and suppressed tumor growth. Conclusion: These results suggest that the miR-4664-3p/PRKCB axis is crucial in NSCLC progression and immune modulation. Hence, MiR-4664-3p is a potential diagnostic and prognostic indicator, as well as therapeutic target in immunotherapy strategies for NSCLC.
Keywords: NSCLC, PRKCB, miR-4664-3p, immune microenvironment, biomarker
Received: 07 Jun 2025; Accepted: 13 Oct 2025.
Copyright: © 2025 Yi, Zhang, Guo, Lu, Gao, Zhao, Su and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jing Lu, 004026@hnucm.edu.cn
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