4.7 Article

Comprehensive Analysis of hsa-miR-654-5p's Tumor-Suppressing Functions

Journal

Publisher

MDPI
DOI: 10.3390/ijms23126411

Keywords

pan-cancer; bioinformatics; target genes; miR-654-5p; epithelial-mesenchymal transition

Funding

  1. National Natural Science Foundation of China [31870855, 31900537]
  2. Natural Science Foundation of Hunan Province, China [2020JJ5657, 2019JJ50731]

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This study investigates the specific roles of hsa-miR-654-5p in lung cancer and demonstrates its tumor-suppressing roles and prognostic values. The abundance of miR-654-5p is significantly elevated in LUAD tissues and correlates with patients' survival. In vitro experiments show that miR-654-5p inhibits the epithelial-mesenchymal transition (EMT) process, cell proliferation, and migration in lung cancer cells. The study also identifies potential target genes of miR-654-5p and develops a risk scoring model for assessing prognosis.
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.

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