ArticleHistology and histopathology2022
MicroRNA-146b-5p/EPHA7 axis regulates cell invasion, metastasis, proliferation, and temozolomide-induced chemoresistance via regulation of IRAK4/TRAF6/NF-κB signaling pathway in aggressive pituitary adenoma.
Article in Histology and histopathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- The Transcription Factor SOX6 Regulates Autophagy Levels Through LAMP5 to Inhibit the Development of Pituitary Adenomas.Applied biochemistry and biotechnology · 2026Article
- Regulatory mechanisms of microRNAs in endocrine disorders and their therapeutic potential.Frontiers in genetics · 2023Review
- Recent advances in understanding and managing pituitary adenomas.Faculty reviews · 2023Review
- Review
- The role of EphA7 in different tumors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- miR-203, fine-tunning neuroinflammation by juggling different components of NF-κB signaling.Journal of neuroinflammation · 2022Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAggressive pituitary adenoma (APA) is a huge challenge for neurosurgeons. Temozolomide (TMZ) is conventionally used in chemotherapy against APA, but acquired resistance developed during long-term therapy limits its benefits. MiRNA-146b-5p has been confirmed to inhibit tumor metastasis. This study aimed to explore the underlying biological functions of miRNA-146b-5p in APA.
methodsSixty confirmed APA tissues and corresponding adjacent normal tissues were collected. We established a TMZ-resistant cell line (GH3/TMZ) by exposing GH3 cells to gradually increasing doses of TMZ for 5 months. Cell Counting Kit-8 assay, flow cytometric analysis, RNA pull-down assay, 5-ethynyl-20-deoxyuridine assay, dual-luciferase reporter gene assay, wound healing assay, and invasion assay were used to explore the malignant biological characteristics of cells. Immunohistochemistry (IHC), western blotting analysis, and real-time quantitative PCR (qRT-PCR) were used to analyze the expression level of related proteins and nucleic acids.
resultsThe expression of miRNA-146b-5p was down-regulated not only in APA tissues but also in PA cell lines compared with the matched adjacent non-tumor tissues or normal human astrocyte (NHA) cells. Low expression of miRNA-146b-5p was notably associated with poorer disease-free survival rate (P=0.032), overall survival rate (P=0.039), larger tumor size (P=0.028), poorer Knosp grade (P=0.020), and poorer Hardy grade (P=0.006) in APA patients. MiRNA-146b-5p negatively regulated cell proliferation, invasion, migration, and induced apoptosis in GH3 cells. Overexpression of miRNA-146b-5p suppressed IRAK4 and TRAF6 protein expression and negatively regulated NF-κB phosphorylation. The restoration of EPHA7 expression in GH3 cells notably reversed the inhibitory effects of miRNA-146b-5p. MiRNA-146b-5p expression was significantly down-regulated and EPHA7 gene expression was significantly up-regulated in GH3/TMZ cells, compared to the parental cell line. Similarly, EPHA7 was up-regulated, while the miRNA-146b-5p level was down-regulated in chemoresistance tissues more than in chemosensitive tissues. The autophagic activity was decreased markedly with increasing miRNA-146b-5p expression, while it was enhanced after Lv-EPHA7 treatment in GH3/TMZ cells.
conclusionsMiRNA-146b-5p can inhibit EPHA7 expression, suppress the IRAK4/TRAF6/NF-κB signaling pathway, and weaken PA cell invasion, metastasis, proliferation, and TMZ-induced chemoresistance in vitro.
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