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Published on: March 30, 2019
Comprehensive Analysis of hsa-miR-654-5p's Tumor-Suppressing Functions
Chuanyang Liu1, Lu Min1, Jingyu Kuang1
1Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha 410073, China.
Abstract:
The pivotal roles of miRNAs in carcinogenesis, metastasis, and prognosis have been demonstrated recently in various cancers. This study intended to investigate the specific roles of hsa-miR-654-5p in lung cancer, which is, in general, rarely discussed. A series of closed-loop bioinformatic functional analyses were integrated with in vitro experimental validation to explore the overall biological functions and pan-cancer regulation pattern of miR-654-5p. We found that miR-654-5p abundance was significantly elevated in LUAD tissues and correlated with patients' survival. A total of 275 potential targets of miR-654-5p were then identified and the miR-654-5p-RNF8 regulation axis was validated in vitro as a proof of concept. Furthermore, we revealed the tumor-suppressing roles of miR-654-5p and demonstrated that miR-654-5p inhibited the lung cancer cell epithelial-mesenchymal transition (EMT) process, cell proliferation, and migration using target-based, abundance-based, and ssGSEA-based bioinformatic methods and in vitro validation. Following the construction of a protein-protein interaction network, 11 highly interconnected hub genes were identified and a five-genes risk scoring model was developed to assess their potential prognostic ability. Our study does not only provide a basic miRNA-mRNA-phenotypes reference map for understanding the function of miR-654-5p in different cancers but also reveals the tumor-suppressing roles and prognostic values of miR-654-5p.
Insights
This study reveals microRNA-654-5p (miR-654-5p) acts as a tumor suppressor in lung adenocarcinoma (LUAD). Elevated miR-654-5p inhibits cancer cell growth, migration, and epithelial-mesenchymal transition, offering prognostic value.
Area of Science:
- Molecular Oncology
- Cancer Genomics
- Biomarker Discovery
Background:
- MicroRNAs (miRNAs) play crucial roles in cancer development, metastasis, and patient prognosis.
- The specific functions of hsa-miR-654-5p in lung cancer remain largely underexplored.
- Understanding miRNA roles is vital for advancing cancer diagnostics and therapeutics.
Purpose of the Study:
- To investigate the biological functions and regulatory patterns of hsa-miR-654-5p in lung cancer.
- To identify potential targets and pathways regulated by miR-654-5p.
- To evaluate the prognostic significance of miR-654-5p in lung adenocarcinoma (LUAD).
Main Methods:
- Integrated bioinformatics analyses (functional, target prediction, ssGSEA) with in vitro experimental validation.
- Identified miRNA-mRNA interactions and constructed protein-protein interaction networks.
- Developed a five-gene risk scoring model for prognostic assessment.
Main Results:
- miR-654-5p was significantly upregulated in LUAD tissues and correlated with patient survival.
- Identified 275 potential targets, validating the miR-654-5p-RNF8 axis.
- Demonstrated miR-654-5p exhibits tumor-suppressive functions by inhibiting LUAD cell proliferation, migration, and epithelial-mesenchymal transition (EMT).
Conclusions:
- miR-654-5p acts as a tumor suppressor in lung cancer, inhibiting key oncogenic processes.
- miR-654-5p holds significant prognostic value for LUAD patients.
- Provides a foundational reference map for miR-654-5p function across various cancers.
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