Abstract
BackgroundAccumulating data have established that microRNAs (miRNAs) play significant regulatory roles in the carcinogenesis and progression of ovarian cancer (OC). MiR-425-5p was reported to function in various tumors. However, the roles and underlying mechanism of miR-425-5p involvement in OC development and progression are unclear.MethodsA comprehensive strategy of data mining, computational biology, and real-time polymerase chain reaction was employed to identify the involvement of miR-425-5p in OC progression. The effect of miR-425-5p on the proliferation, migration, and invasion of OC cells was determined using Cell Counting Kit-8, wound-healing, and Matrigel invasion assays, respectively. Luciferase assay was performed to evaluate the interactions between miR-425-5p and MAGI2-AS3 or AFF4.ResultsmiR-425-5p was significantly up-regulated in OC tissues and cells. The luciferase reporter assay revealed that miR-425-5p was negatively regulated by MAGI2-AS3. Silencing miR-425-5p inhibited the proliferation, migration, and invasion of OC cells in vitro. Bioinformatics analysis and luciferase reporter assay revealed that AFF4 was the target gene of miR-425-5p. Moreover, AFF4 expression was significantly decreased in OC and was closely related to the good prognosis of patients with OC. AFF4 overexpression inhibited the proliferation, migration, and invasion of OC cells in vitro. By contrast, silencing AFF4 promoted the proliferation, migration, and invasion of OC cells in vitro. Finally, AFF4 suppression rescued the inhibitory effect of silencing miR-425-5p on the proliferation, migration, and invasion of OC cells.ConclusionTo the best our knowledge, this is the first study to demonstrate that miR-425-5p overexpression in OC is negatively regulated by MAGI2-AS3. Moreover, miR-425-5p promotes the proliferation, migration, and invasion of OC cells by targeting AFF4, suggesting that miR-425-5p/AFF4 signaling pathway represented a novel therapeutic target for patients with OC.
Highlights
Ovarian cancer (OC) is one of the major malignancies of the female reproductive system, and it has the highest incidence rate among all gynecological malignancies worldwide
MAGI2-AS3 was detected in three ovarian cancer (OC) cell lines (A2780, SKOV3, and ES-2) and IOSE-80 cells and the results demonstrated that MAGI2-AS3 expression was significantly lower in A2780, SKOV3, and ES-2 cells than in IOSE-80 cells (Fig. S1B)
The results presented that only miR-425-5p displayed significant upregulation in OC tissues compared with that in ovarian normal tissues (Fig. 1B)
Summary
Ovarian cancer (OC) is one of the major malignancies of the female reproductive system, and it has the highest incidence rate among all gynecological malignancies worldwide. Given the advances in high-resolution microarray and massively parallel sequencing technology, emerging evidence indicates that microRNAs (miRNAs) play complex and extensive roles in the development and progression of various cancers [3]. Studies have reported the involvement of miR-425-5p in various cancer processes, and it acts as a tumor suppressor or promoter [4, 5]. The exact roles and underlying mechanism of miR-425-5p function in OC are still unclear. Accumulating data have established that microRNAs (miRNAs) play significant regulatory roles in the carcinogenesis and progression of ovarian cancer (OC). The roles and underlying mechanism of miR-425-5p involvement in OC development and progression are unclear
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