MicroRNA‑598 inhibits the growth of triple negative breast cancer cells by targeting JAG1

Abstract

Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor outcome. The discovery that dysregulated microRNAs (miRNAs) play an important role in tumor progression has led to the suggestion that miRNAs (miRs) could be a potential target for the treatment of TNBC. In the present study, it was demonstrated that miR-598 expression was significantly decreased in TNBC tissues and was related to the degree of lymph node metastasis of patients with TNBC. Ectopic expression of miR-598 suppressed viability and colony formation, as well as increased the apoptosis of TNBC cells. To further understand the functional mechanism of action underlying miR-598 in TNBC, targets of miR-598 were predicted with the miRDB bioinformatics tool. Jagged 1 (JAG1) was identified as a direct target of miR-598, possessing a binding site for miR-598 in its 3'-untranslated region. Overexpression of miR-598 inhibited the expression of JAG1 in TNBC cells. In addition, JAG1 was highly expressed in TNBC tissues and its expression was negatively correlated with the expression of miR-598. Overexpression of JAG1 significantly attenuated the inhibitory effects of miR-598 on the proliferation and colony formation of TNBC cells. Collectively, these results provided novel insights into the functional mechanism of action for the miR-598/JAG1 pathway in the development of TNBC.

Hypoxia promotes metastasis by relieving miR-598-3p-restricted glycolysis in gastric cancer

“…However, due to the tumor-speci c and manifold in uence of hypoxia and the divergence of miRNAs and vice versa, the crosstalk between hypoxic signaling and miRNA biogenesis is still relatively unexplored, and the potential therapeutic setting remains to be established. Studies have shown that miR-598 is a tumor suppressor and is downregulated in triple-negative breast cancer [11], retinoblastoma [7], osteosarcoma [12], colorectal cancer [13] and gastric cancer [14]. In addition, miR-598 was shown to suppress the proliferation and metastasis of multiple tumors and was associated with poor prognosis.…”

Inhibitory effect of miR342 on the progression of triple-negative breast cancer cells in vitro and in the mice model

“… 5 Moreover, the role of miR598 in the repression of TNBC was triggered via targeting JAG1. 6 It was demonstrated that intravenous injection of miR206 robustly reduced the mass of xenograft tumors of TNBC. 7 In addition, eight weeks after transplantation of TNBC cells transfected with miR355 to nude mice, slower tumor growth compared to the control group was detected.…”