MicroRNA-433 targets AKT3 and inhibits cell proliferation and viability in breast cancer

Abstract

Abstract. Breast cancer is the most frequently diagnosed malignancy in women. However, the molecular mechanisms underlying breast cancer pathogenesis are not fully understood. The present study examined the role of miR-433 in breast cancer and investigated its underlying molecular mechanisms of action. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to analyze the level of microRNA (miRNA/miR)/mRNA and protein expression, respectively. Additionally, MTT assay was used to determined cell proliferation and viability. Cell apoptosis was measured by flow cytometry. A dual-luciferase reporter assay was used to confirm the identity of the downstream target of miR-433. The results revealed that miR-433 was downregulated in breast cancer tissues and cell lines. Overexpression of miR-433 inhibited cell proliferation and cell viability in BT-549 cells, whereas downregulation of miR-433 increased cell proliferation and cell viability in MDA-MB-231 cells. Further flow cytometry analysis revealed that miR-433 was able to induce apoptosis and also alter the levels of proteins expression of B-cell lymphoma-2 and Bcl-associated X. Bioinformatics analysis showed that RAC-γ serine/threonine-protein kinase (AKT3) was one of the downstream targets of miR-433, and luciferase reporter assay further confirmed that AKT3 is a direct target of miR-433. The knockdown of AKT3 was able to inhibit proliferation and viability in BT-549 cells. Overexpression of AKT3 prevented the inhibitory effects of miR-433 on proliferation and viability in BT-549 cells. The level of AKT3 mRNA expression was upregulated in breast cancer tissues compared with normal tissues and was inversely correlated with miR-433 expression levels. In summary, the results of the present study results indicate that the tumor-suppressive role of miR-433 may be mediated by regulating AKT3. miR-433 may therefore serve as a potential therapeutic target for breast cancer.

Specific microRNA signatures in exosomes of triple-negative and HER2-positive breast cancer patients undergoing neoadjuvant therapy within the GeparSixto trial

“…Moreover, miR-433 repressed Rap1a, a small G protein of the Ras guanosine triphosphatase (GTPase) superfamily that activates the MAPK signaling pathway, and thus repressed cell migration and proliferation and induced apoptosis in BC [ 34 ]. In addition, miR-433 targeted AKT3 in BC [ 35 ]. These findings highlight miR-422a and miR-433 as tumor suppressor genes.…”

Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis

“…Specifically, many lncRNAs act as sponges in the regulation of miRNA target genes involved in OSCC carcinogenesis [21,22]. miR-433, a wellcharacterized miRNA, was found to be a tumor suppressor in different neoplasms [23,24].…”

RP11-480I12.5-004 Promotes Growth and Tumorigenesis of Breast Cancer by Relieving miR-29c-3p-Mediated AKT3 and CDK6 Degradation

“…Both AKT3 and CDK6 have been previously reported to promote growth of breast cancer. 33,34 MS2-RIP assay also showed miR-29c-3p-mediated the ceRNA crosstalk between RP11-480I12.5-004 and CDK6 or AKT3 in breast cancer cells.…”