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MEG3/MIR-376B-3P/HMGA2 axis is involved in pituitary tumor invasiveness
Dimin Zhu1, Zheng Xiao1, Zongming Wang1
11Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital of Sun Yat-sen University; and.
Objective:
To date, long noncoding RNAs (lncRNAs) have proven to function as key regulators in tumorigenesis. Among these lncRNAs, MEG3 displays low levels in various neoplasms and tumor cell lines. However, the regulatory mechanism of MEG3 and MIR-376B-3P, one of the microRNAs from downstream gene clusters of the DLK1-MEG3 locus, remains insufficiently defined.
Methods:
The authors used quantitative real-time polymerase chain reaction analysis to analyze whether decreased MEG3 and MIR-376B-3P expression levels were associated with the invasiveness of clinical nonfunctioning pituitary adenomas (CNFPAs) in 30 patients. Furthermore, functional experiments unveiled the pathophysiological role of MEG3, MIR-376B-3P, and HMGA2 in pituitary-derived folliculostellate (PDFS) cell lines. Moreover, dual-luciferase reporter assay, Western blot analysis, and immunofluorescence were applied to reveal the correlations among MEG3, MIR-376B-3P, and HMGA2.
Results:
MEG3 and MIR-376B-3P were decreased in patients with CNFPA, and their transcriptional levels were highly associated with invasive CNFPAs. Moreover, excessive expression of MEG3 and MIR-376B-3P inhibited tumorigenesis and promoted apoptosis in PDFS cells. Importantly, the authors found that MEG3 acted as an enhancer of MIR-376B-3P expression. Furthermore, as a target gene of MIR-376B-3P, HMGA2 served as an oncogene in pituitary adenoma and could be negatively regulated by MEG3 via enriching MIR-376B-3P.
Conclusions:
This study offers a novel mechanism of an MEG3/MIR-376B-3P/HMGA2 regulatory network in CNFPAs, which may become a breakthrough for anticancer treatments.
Insights
Decreased MEG3 and MIR-376B-3P levels correlate with invasive pituitary adenomas. This MEG3/MIR-376B-3P/HMGA2 network offers potential new anticancer strategies.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are key regulators in tumorigenesis.
- MEG3 lncRNA levels are often reduced in various cancers.
- The regulatory roles of MEG3 and MIR-376B-3P in pituitary adenomas are not fully understood.
Purpose of the Study:
- To investigate the association between MEG3 and MIR-376B-3P expression and the invasiveness of clinical nonfunctioning pituitary adenomas (CNFPAs).
- To elucidate the functional roles of MEG3, MIR-376B-3P, and HMGA2 in pituitary-derived folliculostellate (PDFS) cells.
- To uncover the regulatory network involving MEG3, MIR-376B-3P, and HMGA2.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to assess gene expression.
- Functional experiments in PDFS cell lines.
- Dual-luciferase reporter assays, Western blot, and immunofluorescence to determine molecular interactions.
Main Results:
- MEG3 and MIR-376B-3P expression was decreased in CNFPA patients and correlated with invasiveness.
- Overexpression of MEG3 and MIR-376B-3P inhibited tumor growth and promoted apoptosis in PDFS cells.
- MEG3 enhances MIR-376B-3P expression, which targets and negatively regulates the oncogene HMGA2.
Conclusions:
- A novel MEG3/MIR-376B-3P/HMGA2 regulatory network was identified in CNFPAs.
- This network provides a potential therapeutic target for pituitary adenoma treatment.
- Understanding this mechanism may lead to breakthroughs in anticancer therapies.
