Introductions: Regeneration is the process of the restoration of an injured organ, extremity, or tissue without functional loss. Axolotl, a species of aquatic salamander, can perform successful regeneration after a non-lethal injury to internal organs, the central nervous system, and extremities. miRNAs targeting mRNAs have essential roles in post-transcriptional regulation by decreasing the translational level. This study was an investigation of changes in the miRNA profile and the effect of miRNAs on molecular pathways during tail regeneration.

Methods: 60 axolotls 6 to 8 cm in length was amputated and the animals were randomly divided into 4 groups. Tissue samples were taken just after amputation (day 0 sample), and on the first, fourth, and seventh day of regeneration. miRNAs were identified in the collected samples using next generation sequencing. Among the identified miRNAs, those demonstrating significant change at different stages of regeneration were analyzed to explore the pathways regulated.

Results: Of the identified miRNAs, 52 that changed (increased or decreased) by 1.5 times or more were used in molecular pathway analysis. It was found that miRNAs upregulated during regeneration controlled homeostatic pathways, while downregulated miRNAs controlled the cell cycle and cell cycle regulating pathways.

Discussion and Conclusion: miRNAs act in fundamental processes, such as homeostasis, development, growth, and regulation of disease. A shift in the miRNA profile is necessary to achieve progress and the successful accomplishment of regeneration. In this study, the dynamic alterations of increased and decreased miRNAs levels were identified and the putative effects on molecular pathways were examined.