MicroRNA hsa-miR-623 directly suppresses MMP1 and attenuates IL-8-induced metastasis in pancreatic cancer

Abstract

Matrix metalloproteinase‑1 (MMP1) participates in the metastasis of pancreatic cancer, and its expression can be regulated by endogenous microRNAs (miRs/miRNAs) and exogenous inflammatory factors. Whether miRNAs that potentially modulate MMP1 expression can also attenuate the pro‑metastatic effects of its inducer on pancreatic cancer is yet to be completely elucidated. In the present study, a systematic analysis including in silico and bioinformatics analyses, a luciferase reporter assay and an RNA electrophoretic mobility shift assay (EMSA), were used to investigate the interaction between miRNAs and MMP1 mRNA. In addition, wound‑healing assays, Transwell assays and xenograft nude mouse models were implemented to investigate the antitumor activities exerted by candidate miRNAs. As a result, hsa‑miR‑623 was screened as a candidate miRNA that interacts with the MMP1 transcript, and an inverse correlation between the expression of hsa‑miR‑623 and MMP1 was observed in human pancreatic cancer tissue samples. The EMSA confirmed that hsa‑miR‑623 was able to directly bind to its cognate target within the 3'‑untranslated region of the MMP1 transcript. In addition, transfection of hsa‑miR‑623 mimics into PANC‑1 and BXPC‑3 cell lines markedly inhibited the expression of MMP1 at the mRNA and protein levels, and attenuated IL‑8‑induced MMP1 expression. hsa‑miR‑623 also decreased IL‑8‑induced epithelial‑mesenchymal transition in PANC‑1 and BXPC‑3 cells via the underlying mechanism of inhibition of ERK phosphorylation. Consequently, hsa‑miR‑623 inhibited pancreatic cancer cell migration and invasion in vitro and metastasis in vivo. The results of the present study suggest that hsa‑miR‑623 represents a novel adjuvant therapeutic target to prevent metastasis in pancreatic cancer.