RESUMEN
Cervical cancer (CC) remains a highly prevalent cancer and mortality globally among women globally. The aim of the present study was to assess the ability of miR-374b to regulate CC cells through JAM-2, whilst exploring whether the underlying mechanism and its relation to the p38/ERK signaling pathway. During the study, microRNA-374b (miR-374b) was observed to have been expressed at a low level among CC tissues. Hence, a series of miR-374b mimics, miR-374b inhibitors, siRNA against JAM-2, SB202190 (an inhibitor for p38), and PD98059 (an inhibitor for ERK) were introduced to treat CC Siha cells and normal cervical Ect1/E6E7 cells. MTT, flow cytometry, scratch test, and transwell assays were applied to determine cell viability, apoptosis, migration, and invasion. The inhibitory role of the p38/ERK signaling pathway was observed in the CC cells treated with miR-374b mimics or siRNA against JAM-2. miR-374b mimic exposure was found to reduce cell viability, migration, and invasion, but induce apoptosis. MiR-374b inhibitor exposure was observed to have induced effects on the CC cells in a contrary manner to those induced by that of the miR-374b mimics. The key findings of the study demonstrated that miR-374b significantly inhibits cell proliferation, migration, and invasion through the blockade of the p38/ERK signaling pathway activation, as well as negatively binding to JAM-2, highlighting its potential as a therapeutic target for CC.
Asunto(s)
Apoptosis/genética , Moléculas de Adhesión Celular/metabolismo , Sistema de Señalización de MAP Quinasas , MicroARNs/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Adulto , Secuencia de Bases , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica , Regulación hacia Arriba/genéticaRESUMEN
OBJECTIVE: The study aimed to investigate cyclin-dependent kinase 14 (CDK14) and its co-function with Wnt signaling pathway on cell proliferation, migration and invasion in ovarian cancer. METHODS: CDK14 expressions were detected by quantitative real-time polymerase chain reaction. The expressions c-Myc, cyclinD1, PFTK1, ki67 and OGT were examined by Western blot. MTT assay was applied to observe cell proliferation after transfection of pEGFP-N1/CDK14-siRNA and pEGFP-N1 into SKOV3 cells, and scratch test and Transwell assay to observe invasion and migration ability. Transfected tumor model in nude mice was established. RESULTS: CDK14 was upregulated in the ovarian cancer tissues and cell lines (both p < 0.05). Expressions of downstream molecules in Wnt signaling pathway as well as the proliferation, invasion and migration ability of the SKOV3 cells were reduced when CDK14 was inhibited (all p < 0.05). The expression of ß-catenin in the nucleus was also decreased when CDK14 was inhibited (p < 0.05). In the transfected tumor model of nude mice, the results showed, compared with the pEGFP-N1 group and blank control group, that the expressions of c-Myc, cyclinD1, PFTK1, ki67 and OGT in the pEGFP-N1/CDK14-siRNA group in the transplantation tumor tissues decreased significantly (all p < 0.05). CONCLUSION: CDK14 suppression-mediated Wnt signaling pathway can inhibit cell proliferation, invasion and migration in ovarian cancer.