Long non-coding RNA MEG3 acts as a tumor inhibitor in human cancer

Introduction: The role of MEG3 in human cancers remains incompletely understood. Objective: In this study, we elucidate the tumor-suppressive function of MEG3 across multiple cancer types, including ovarian cancer. Methods: We systematically analyzed MEG3 expression in both tumor and normal tissues using publicly available databases to investigate its regulatory implications for clinical prognosis, pathological stage, tumor purity, chemotherapy resistance, and immune cell infiltration. Furthermore, we explored the underlying regulatory mechanisms of MEG3 by predicting upstream transcription factors and conducting downstream functional enrichment analyses. Results: Our findings demonstrate that MEG3 expression is significantly downregulated in tumor tissues compared to normal counterparts. Moreover, MEG3 expression is associated with overall survival, relapse-free survival, and tumor, node, metastasis staging across several malignancies. Notably, higher MEG3 expression is negatively correlated with tumor purity and chemotherapy resistance. We identified SPI1 as a potential upstream transcription factor regulating MEG3 expression. Functional enrichment analysis revealed that MEG3 may exert its tumor-suppressive effects through the modulation of the Hippo signaling pathway. In addition, MEG3 methylation was found to regulate the expression of genes involved in the cell cycle of ovarian cancer cells and modulate the ovarian cancer microenvironment by influencing immune cell infiltration. Conclusion: These results collectively suggest that MEG3 may serve as a tumor suppressor and represent a promising therapeutic target in human cancers.