Photo Credit: OGphoto

The following is a summary of “Deep sequencing reveals distinct microRNA-mRNA signatures that differentiate pancreatic neuroendocrine tumor from non-diseased pancreas tissue,” published in the April 2025 issue of BMC Cancer by Matyasovska et al. 

Pancreatic neuroendocrine tumors (PanNETs) represent a heterogeneous group of neoplasms with limited molecular biomarkers to guide individualized treatment approaches. Although transcriptomic analyses of both microRNAs (miRs) and messenger RNAs (mRNAs) have shown promise in classifying PanNETs and identifying patients who may benefit from specific therapies, their integrative potential remains underexplored. Given the critical role of miRs in regulating mRNA expression, this study aimed to construct high-confidence miR–mRNA interaction networks to deepen the understanding of PanNET molecular biology and uncover novel regulatory mechanisms and potential biomarkers.

Deep sequencing of both miRs and mRNAs was performed on six well-differentiated, low-grade but high-risk PanNET tissue samples and compared to seven non-tumor pancreatic tissue controls. Differentially expressed miRs and mRNAs were identified through comparative expression analysis. To develop integrative interaction networks, the differentially expressed mRNAs were cross-referenced with in silico–predicted mRNA targets of both highly expressed and minimally expressed miRs, yielding candidate miR–mRNA regulatory pairs with high biological relevance.

Gene ontology and pathway enrichment analyses of the miR–mRNA pairs revealed multiple dysregulated cellular pathways not apparent through mRNA profiling alone. Specifically, interactions involving miR-7 and members of the Regenerating gene family were associated with disrupted neuroendocrine function. Dysregulation of cell adhesion pathways was observed through associations between miR-216 family members and key adhesion molecules such as NLGN1, NCAM1, and CNTN1, as well as miR-670 and tight junction proteins CLDN1 and CLDN2. Metabolic dysfunction was suggested by interactions of miR-670 with BCAT1 and MPST, and miR-129 with CTH, implicating these pairs in altered amino acid metabolism and oxidative stress responses.

The integration of miR and mRNA expression profiles into miR–mRNA interaction networks revealed novel pathways and regulatory mechanisms underlying PanNET pathogenesis that are not detectable through mRNA analysis alone. These findings not only enhance the biological understanding of PanNETs but also highlight a set of candidate interactions that may serve as future diagnostic or predictive biomarkers. Further functional validation and clinical correlation studies are warranted to determine the translational potential of these regulatory networks in personalized PanNET management.

Source: bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14043-w