In Silico Identification of circPIM1/miR-16-5p/miR-195-5p/PIM1 Feed-Forward Loop in Recurrent Grade 2 Meningioma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• A 34-transcript biomarker (34HR-MNG) predicts meningioma (MNG) tumor outcome, including recurrence.
• Understanding the molecular mechanisms behind 34HR-MNG transcript regulation is crucial for MNG recurrence prediction.

Purpose of the Study:

• To construct a competitive endogenous RNA (ceRNA) network to elucidate molecular mechanisms regulating 34HR-MNG transcripts.
• To identify the functional role of this network in MNG recurrence.

Main Methods:

• In silico construction of a ceRNA network using MiRTarbase and ENCORI databases.
• Correlation analysis of circRNA host gene expression with MNG clinical/molecular features (RNA-seq dataset GSE189672).
• Validation of circRNA and host gene expression via qRT-PCR.

Main Results:

• Pim-1 proto-oncogene, serine/threonine kinase (PIM1) was upregulated in WHO grade 2 vs. grade 1 and recurrent vs. non-recurrent WHO grade 2 MNGs.
• PIM1 expression correlated with Ki-67 and NF2 in recurrent WHO grade 2 MNGs.
• CircRNAs 0076215 and 0076216, derived from PIM1, sponge tumor-suppressive miRNAs (16-5p, 195-5p), leading to PIM1 upregulation.

Conclusions:

• PIM1 acts as an oncogene implicated in WHO grade 2 MNG recurrence.
• The identified ceRNA network, including PIM1, circRNAs 0076215/0076216, and miRNAs 16-5p/195-5p, drives PIM1 upregulation via a feed-forward loop, contributing to MNG recurrence.