miR-30b suppresses the progression of breast cancer through inhibition of the PI3K/Akt signaling pathway by targeting Derlin-1

MicroRNAs (miRNAs) play an essential role in the initiation, progression and metastasis of breast cancer. It has been confirmed that miR-30b is involved in various cancers. However, the specific involvement of miR-30b on breast cancer metastasis remains unknown. In the current study, we aimed to investigate the role of miR-30b in the progression and metastasis of breast cancer in vitro.

Our data demonstrated that miR-30b suppresses the progression and metastasis of breast cancer via inhibition of the PI3K/Akt signaling pathway by targeting Derlin-1 in vitro. This suggests that miR-30b might be a novel potent target for breast cancer therapy.

We up-regulated the expression of miR-30b in breast cancer cell lines SKBR3 and MDA-MB-231 by transfecting pCMV-miR-30b vector. CCK8, colony formation, Transwell, and flow cytometry assays were used to examine cell proliferation, migration, invasion and apoptosis, respectively. A dual-luciferase reporter assay was performed to identify the relationship between miR-30b and the target gene. Western blot assay was used to detect related proteins.

Our data showed that the overexpression of miR-30b significantly inhibited proliferation, migration and invasion abilities in SKBR3 and MDA-MB-231 cells. Meanwhile, overexpression of miR-30b induced cell apoptosis for both SKBR3 and MDA-MB-231 cells by regulating the expression of apoptosis-related proteins (Bcl-2, Bax, active Caspase-3, and Caspase-9). Moreover, miR-30b inhibited the activation of the PI3K/Akt signaling pathway by decreasing the phosphorylation levels of Akt and mTOR. Furthermore, we determined that miR-30b could down-regulate the expression of Derlin-1 in a post-transcriptional manner by employing the dual-luciferase reporter and western blot assays. Further analysis demonstrated that depletion of Derlin-1 inhibited Akt phosphorylation, and Derlin-1 could restore the effect of miR-30b on Akt. In addition, the CCK8 assay showed that Derlin-1 could partly reverse the inhibition of cell proliferation of SKBR3 and MDA-MB-231 cells mediated by miR-30b. Conclusions: Our data demonstrated that miR-30b suppresses the progression and metastasis of breast cancer via inhibition of the PI3K/Akt signaling pathway by targeting Derlin-1 in vitro. This suggests that miR-30b might be a novel potent target for breast cancer therapy.