Identification of phosphoinositide-associated microRNAs reveals candidates with potential roles in cancer signaling

Jany Valdes; Jaime A. Ceja; Andrea Bayona; Enrique Castaño de la Serna; Jany Valdes; Jaime A. Ceja; Andrea Bayona; Enrique Castaño de la Serna

doi:10.3934/molsci.2025024

AIMS Molecular Science

2025, Volume 12, Issue 4: 438-452. doi: 10.3934/molsci.2025024

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Identification of phosphoinositide-associated microRNAs reveals candidates with potential roles in cancer signaling

Integrative Biology Unit, Scientific Research Center of Yucatan, Calle 43, Number 130, Chuburná de Hidalgo, Mérida CP 97205, Yucatan, Mexico

Received: 25 June 2025 Revised: 13 November 2025 Accepted: 02 December 2025 Published: 10 December 2025

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and have been associated with pathological processes, including oncogenesis. In this study, the interaction between miRNAs and phosphoinositides, particularly phosphatidylinositol 4,5-bisphosphate (PIP2), was explored by pull-down assays, followed by RNA sequencing (RNA-seq) analysis in HeLa cells. Four miRNAs with specific affinity toward PIP2 and PI4P were identified, including hsa-miR-3181-1, hsa-miR-4720, hsa-miR-142, and hsa-miR-940. Structural analysis suggested that the interaction with lipids is mediated by secondary conformations rather than by sequence homology. Furthermore, two of these miRNAs were present in human blood fractions, with particular emphasis on hsa-miR-142, whose plasma distribution suggests a potential role as a phosphoinositide-mediated long-range signaling molecule. These miRNAs have been associated with tumor-related processes, suggesting a potential, although not yet confirmed, relevance as noninvasive biomarkers or therapeutic targets in cancer.
- microRNA,
- phosphoinositides,
- cancer,
- bloods cells,
- PIP2,
- PI4P
Citation: Jany Valdes, Jaime A. Ceja, Andrea Bayona, Enrique Castaño de la Serna. Identification of phosphoinositide-associated microRNAs reveals candidates with potential roles in cancer signaling[J]. AIMS Molecular Science, 2025, 12(4): 438-452. doi: 10.3934/molsci.2025024

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Abstract

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and have been associated with pathological processes, including oncogenesis. In this study, the interaction between miRNAs and phosphoinositides, particularly phosphatidylinositol 4,5-bisphosphate (PIP2), was explored by pull-down assays, followed by RNA sequencing (RNA-seq) analysis in HeLa cells. Four miRNAs with specific affinity toward PIP2 and PI4P were identified, including hsa-miR-3181-1, hsa-miR-4720, hsa-miR-142, and hsa-miR-940. Structural analysis suggested that the interaction with lipids is mediated by secondary conformations rather than by sequence homology. Furthermore, two of these miRNAs were present in human blood fractions, with particular emphasis on hsa-miR-142, whose plasma distribution suggests a potential role as a phosphoinositide-mediated long-range signaling molecule. These miRNAs have been associated with tumor-related processes, suggesting a potential, although not yet confirmed, relevance as noninvasive biomarkers or therapeutic targets in cancer.

Acknowledgments

We thank Wilma A. González-Kantún for her technical assistance.

Conflict of interest

The authors declare no conflict of interest in this paper.

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