MiR-320a Acts as a Tumor Suppressor in Somatotroph Pituitary Neuroendocrine Tumors by Targeting BCAT1.

Autor:	Zhao S; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China., Li B; Department of Neurosurgery, Peking University People's Hospital, Beijing, China., Gao H; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China., Zhang Y; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; Beijing Institute for Brain Disorders Brain Tumor Center, Beijing, China.
Jazyk:	angličtina
Zdroj:	Neuroendocrinology [Neuroendocrinology] 2024; Vol. 114 (1), pp. 14-24. Date of Electronic Publication: 2023 Aug 17.
DOI:	10.1159/000533549
Abstrakt:	Introduction: Aberrant miR-320a has been reported to be involved in the tumorigenesis of several cancers. In our previous study, we identified the low expression of circulating miR-320a in patients with somatotroph pituitary neuroendocrine tumor (PitNET); however, the role of miR-320a in somatotroph PitNET proliferation is still unclear. Methods: Cell viability and colony formation assays were used to detect the effect of miR-320a and BCAT1 on GH3 cells. TargetScan was used to identify the target genes of miR-320a. Dual-luciferase reporter gene assay was used to explore the relation between miR-320a and BCAT1. Transcriptome and proteome analyses were performed between somatotroph PitNETs and healthy controls. The expression level of miR-320a in somatotroph PitNETs were detected by RT-qPCR and Western blot. Results: miR-320a mimics inhibit cell proliferation, while miR-320a inhibitors promote cell proliferation in GH3 cells. An overlap analysis using a Venn diagram revealed that BCAT1 is the only target gene of miR-320a overexpressed in somatotroph PitNETs compared to healthy controls, as revealed by both microarray and proteomics results. A dual-luciferase reporter gene assay showed that miR-320a may bind to the BCAT1-3'UTR. The transfection of miR-320a mimics downregulated the expression and miR-320a inhibitors and upregulated the expression of BCAT1 in GH3 cells. The interference of BCAT1 expression in GH3 cells downregulated cell proliferation and growth. Pan-cancer analyses demonstrated that high BCAT1 expression often indicates a poor prognosis. Conclusion: Our findings illustrate that miR-320a may function as a tumor suppressor and BCAT1 may promote tumor progression. miR-320a may inhibit the growth of somatotroph PitNETs by targeting BCAT1. (© 2023 S. Karger AG, Basel.)
Databáze:	MEDLINE
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