مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
The Oncogenic Role of lncRNA-PNUTS in Modulating the miR-145-5p/EGFR Axis in Glioblastoma
The Oncogenic Role of lncRNA-PNUTS in Modulating the miR-145-5p/EGFR Axis in Glioblastoma
Elham Ghadami,1,*Masoumeh Razipour ,2
1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Introduction: Introduction:
Glioblastoma multiforme (GBM) is the most aggressive and lethal form of primary brain tumor, characterized by rapid growth, diffuse invasiveness, and resistance to current therapies, leading to a median survival of only 12–15 months. Increasing evidence suggests that dysregulated non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play crucial roles in GBM initiation and progression. lncRNA-PNUTS (PPP1R10) has recently been reported to act as an oncogene in breast and liver cancers, but its potential role in glioblastoma remains largely unknown. Given the importance of miR-145-5p as a tumor suppressor that negatively regulates EGFR, we aimed to investigate the potential lncRNA-PNUTS/miR-145-5p/EGFR regulatory axis in GBM.
Methods: Methods:
Based on bioinformatics prediction, we constructed a putative regulatory network involving lncRNA-PNUTS, miR-145-5p, and EGFR. Human glioblastoma tissue samples and normal brain tissues were collected, and total RNA was extracted using Kiazol reagent according to the manufacturer’s instructions. Complementary DNA (cDNA) was synthesized using the Yekta Tajhiz Azma cDNA Synthesis Kit (Iran). Quantitative expression analysis of lncRNA-PNUTS, miR-145-5p, and EGFR transcripts was performed using Roche LightCycler 96 Real-Time PCR with SYBR Green chemistry. GAPDH and U6 snRNA were used as internal controls for normalization. Statistical analysis was conducted with GraphPad Prism software, and p-values < 0.05 were considered statistically significant.
Results: Results:
The expression analysis revealed that lncRNA-PNUTS and EGFR were significantly upregulated in glioblastoma tissues compared to normal brain samples, while miR-145-5p was markedly downregulated (p < 0.05). Correlation analysis demonstrated an inverse relationship between lncRNA-PNUTS and miR-145-5p expression, as well as between miR-145-5p and EGFR. In contrast, lncRNA-PNUTS expression positively correlated with EGFR levels (p < 0.05). No significant associations were identified between the altered expression levels of lncRNA-PNUTS, miR-145-5p, and EGFR with clinicopathological parameters.
Conclusion: Conclusion:
Our findings suggest that lncRNA-PNUTS functions as a competing endogenous RNA (ceRNA) by sponging miR-145-5p, thereby enhancing EGFR expression and contributing to glioblastoma pathogenesis. This study provides the first evidence of the oncogenic role of lncRNA-PNUTS in glioblastoma and highlights the lncRNA-PNUTS/miR-145-5p/EGFR regulatory axis as a promising molecular pathway for diagnostic and therapeutic interventions. Further functional studies are warranted to explore its potential as a biomarker and therapeutic target in GBM.