Abstract
Our previous study explored the roles of microRNA-424 (miR-424) in the development of endometrial carcinoma (EC) and analyzed the miR-424/E2F7 axis in EC cell growth. In this study, we investigated the status of miR-424 in human endometrial cancer tissues, which were collected from a cohort of Zunyi patients. We found that the expression level of miR-424 was associated with clinical tumor stage, cell differentiation, lymph node metastasis and cell migration ability. Cell function experiments demonstrated that miR-424 overexpression suppressed the invasion and migration abilities of endometrial carcinoma cells in vitro. Bioinformatic predictions and dual-luciferase reporter assays suggested E2F6 as a possible target of miR-424. RT-PCR and western blot assays demonstrated that miR-424 transfection reduced the expression level of E2F6, while inhibiting miR-424 with ASO-miR-424 (antisense oligonucleotides of miR-424) increased the expression level of E2F6. Cell function experiments indicated that E2F6 transfection rescued the EC cell phenotype induced by miR-424. In addition, we also found that E2F6 negatively regulated miR-424 expression in EC cells. In summary, our results demonstrated that the miR-424/E2F6 feedback loop modulates cell invasion, migration and EMT in EC and that the miR-424/E2Fs regulation network may serve as a new and potentially important therapeutic target in EC.
Highlights
Endometrial carcinoma (EC) is the fourth most frequent tumor malignancy in women in the developed world, following breast, colorectal and lung cancer, and recently, its incidence has increased worldwide [1]
The results revealed that miR424 suppressed cell invasion (Figure 2A–2C), migration (Figure 2D–2F) and scratch repair ability (Figure 2G–2J) in HEC-1A and Ishikawa cells; antisense oligonucleotides (ASO)-miR-424 promoted cell invasion, migration and scratch repair in HEC-1A and Ishikawa cells (Figure 2)
Zhang et al reported that miR-424 promotes nonsmall cell lung cancer metastasis by regulating TNFAIP1 [21]
Summary
Endometrial carcinoma (EC) is the fourth most frequent tumor malignancy in women in the developed world, following breast, colorectal and lung cancer, and recently, its incidence has increased worldwide [1]. Despite most cases being diagnosed in the early stages of disease, 28% of patients still have regional or distant metastasis. EC has a low 5-year survival rate at the incurable stages and a high rate of recurrence and metastasis despite recent advances in therapeutic strategies [4]. Targeted molecular therapies provide useful future strategies for controlling endometrial malignancies [5], they are still largely undiscovered. It is important to identify molecular mechanisms involved in the development and progression of EC and to discover novel drug targets
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