Micro RNA-338-3p regulates proliferation, apoptosis, migration, and invasion of ovarian cancer cells through ERBB2
Jing Fang, Jing Chao
2025, 46(3):
527-537.
doi:10.3969/j.issn.1006-7795.2025.03.018
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Objective To investigate the effect of microRNA (miR)-338-3p on the biological behavior of ovarian cancer (OC) cells by targeting human epidermal growth factor receptor 2 (ERBB2). MethodsThe expression levels of miR-338-3p and ERBB2 were collected from the cancerous and adjacent tissues of 45 OC patients. A2780, SKOV3, OVCAR3, and IOSE-80 cells were cultured in vitro, and the expression of miR-338-3p and ERBB2 was analyzed and compared, the targeting relationship between miR-338-3p and ERBB2 was also analyzed. A2780 cells were randomly separated into A2780 group (normal A2780 cells), negative control (NC) group (A2780 cells transfected with miR-NC); miR-338-3p group (transfected with miR-338-3p mimic), PcDNA3.1+miR-338-3p group (transfected with miR-338-3p mimic+pcDNA3.1), and PcDNA3.1-ERBB2 group (transfected with miR-338-3p mimic+pcDNA3.1-ERBB2). The proliferation, apoptosis, invasion, and migration of cells in each group were analyzed, and the expression of ERBB2 protein and proliferation and apoptosis related proteins were measured. A2780 cells were injected into the right axilla of nude mice, and were recorded as model group, NC group, miR-338-3p group, pcDNA3.1+miR-338-3p group, miR-338-3p+ERBB2 group, with 6 cells in each group. After 6 weeks of feeding, the mice were killed and the tumor tissue was taken, and the volume and quality were measured. The expression of ERBB2 in tumor tissues was analyzed by immunohistochemistry. Results The expression of miR-338-3p in OC tissues and cell lines was lower than that in adjacent tissues and IOSE-80 cells, while the expression of ERBB2 mRNA and protein was higher than that in adjacent tissues and IOSE-80 cells (P<0.05). There was a targeting relationship between miR-338-3p and ERBB2, and miR-338-3p negatively regulated ERBB2 expression. After transfection with miR-338-3p mimic, the numbers of cell proliferation, invasion and migration, the expression of ERBB2, B-cellymphoma-2 (Bcl-2), phosphorylation extracellular signal-regulated kinase 1/2 (p-ERK1/2), matrixmetalloproteinase-9 (MMP-9) proteins decreased, while the apoptosis rate and the expression of Bcl-2 associated X (bax) protein increased (P<0.05). Transfection of ERBB2 overexpression plasmid was able to increase the numbers of cell proliferation, invasion and migration, the expression of ERBB2, Bcl-2, p-ERK1/2, MMP-9 proteins, and increase the apoptosis rate and the expression of bax protein (P<0.05). Compared with model group and NC group, tumor mass, volume and ERBB2 expression in tumor tissues of miR-338-3p group were decreased (P<0.05). Compared with miR-338-3p group and pcDNA3.1+miR-338-3p group, ERBB2 expression in tumor tissues of miR-338-3p group was decreased (P<0.05). The tumor mass, volume and the expression of ERBB2 in tumor tissues of miR-338-3p+ERBB2 group were increased (P<0.05). Conclusion miR-338-3p may target and regulate ERBB2, thereby inhibiting the growth and apoptosis of OC cells.