Functions and Mechanisms of Tumor Necrosis Factor-α and Noncoding RNAs in Bone-Invasive Pituitary Adenomas

Abstract

To explore the molecular mechanism and prognosis of bone-invasive pituitary adenomas (BIPA). A total of 274 patients with pituitary adenomas were followed up. Transcriptomic microarrays analysis was performed on 10 pituitary adenomas, including five BIPAs and five non-bone-invasive pituitary adenomas (NBIPA). The targeted molecular markers were validated by qRT-PCR, IHC, ELISA, and osteoclast differentiation. Clinical variable analyses revealed a significant correlation between bone invasion and female sex, large tumor volume, non-gross total resection (NGTR), and tumor regrowth. BIPAs had worse progression-free survival (PFS) than did NBIPAs in the NGTR and nonfunctional pituitary adenoma (NFPA) groups. Gene ontology functional and KEGG pathway analyses showed that the biological processes and pathways were primarily immune and inflammatory pathways. Pathway act work showed that osteoclast differentiation pathway was significantly implicated in the pathway network. BIPAs had higher expression of TNFα than that of NBIPAs on IHC. , TNFα could induce RAW264.7 cells to differentiate into mature osteoclasts, leading to bone destruction. NR_033258, lncRNA SNHG24, miR-181c-5p, and miR-454-3p can regulate TNFα expression. BIPAs had worse PFS than did NBIPAs in the NGTR and NFPA groups. Inflammatory and immune factors play an important role in BIPAs. TNFα can directly induce osteoclast differentiation in BIPAs. NR_033258, lncRNA SNHG24, miR-181c-5p, and miR-454-3p can regulate TNFα expression. TNFα and its related lncRNAs and miRNAs represent potential therapeutic targets for bone-invasive pituitary adenomas in the future. .

Small Nucleolar RNA and Small Nucleolar RNA Host Gene Signatures as Biomarkers for Pancreatic Cancer

“…SNHG24, a prominent regulator of the ceRNA network, was found to be closely linked with the process of GnRH secretion and neuroactive ligand-receptor interaction, and exhibited signi cant correlation with KISS1. Reports suggest that the lncRNA SNHG24 can regulate TNF-α expression, and TNF-α and its associated lncRNA SNHG24 represent potential therapeutic targets for bone-invasive pituitary adenomas in the future [39]. Eckstein et al [40] highlighted a strong correlation between GnRH secretion and the risk of prostate cancer, which directly supports our ndings.…”

Lineage-dependent role of miR-410-3p as oncomiR in gonadotroph and corticotroph pituitary adenomas or tumor suppressor miR in somatotroph adenomas via MAPK, PTEN/AKT, and STAT3 signaling pathways

“…Unpaired t-test *p < 0.05, **p < 0.01, ***p < 0.001 expression. Zhu et al [22]. found that the expression of miR-410-3p was higher in bone-invasive pituitary adenoma compared to nonbone-invasive pituitary adenomas.…”

“…1b, p > 0.05). However, based on analysis of an expression dataset published by Zhu et al [22], miR-410-3p was significantly overexpressed in bone-invasive pituitary adenomas (BIPA) compared to nonbone-invasive pituitary adenomas (NBIPA) (fold change 15.13, p = 0.0031) Fig. 1c.…”

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms

“…A study on invasive pituitary tumors identified that the TNFα network—including genes coding for proteins (TNFα, CCL3, CXCL12, and CCL2), microRNAs (miR-181c-5p and miR-454-3p) and lncRNAs (NR_033258 and lncRNA_SNHG24)—is upregulated in bone-invasive pituitary adenomas compared nonbone-invasive counterparts, suggesting that targeting the TNFα pathway may be beneficial for these invasive tumors ( 320 ).…”