miR‐124 exerts tumor suppressive functions on the cell proliferation, motility and angiogenesis of bladder cancer by fine‐tuning UHRF1

Abstract

UHRF1, an epigenetic factor, is implicated in various cellular processes of tumorigenesis. However, the modulation of UHRF1 expression in human bladder cancer at post‐transcriptional levels remains unclear. Here, we report that miR‐124 suppresses expression of UHRF1 to affect the progression of human bladder cancer through competitive binding of the same region of its 3′‐UTR. We show that compared with corresponding normal tissues, UHRF1 is upregulated and miR‐124 is downregulated in bladder cancer tissues, demonstrating an inverse correlation of miR‐124 and UHRF1. Quantitative PCR and western blot assay demonstrated that over‐expression of miR‐124 resulted in the suppression of UHRF1. Furthermore, luciferase assay revealed that miR‐124 could control the fate of target gene UHRF1 mRNA by binding 3′‐UTR. The rescue experiment confirmed that miR‐124 exerted its biological functions by targeting UHRF1. miR‐124 over‐expression significantly attenuated cellular proliferation, migration, invasion and vasculogenic mimicry in vitro, and tumor growth in vivo. UHRF1 siRNA showed significant inhibitory effects on bladder cancer cells. Collectively, our study demonstrates that miR‐124 can impair the proliferation or metastasis of human bladder cancer cells by down‐regulation of UHRF1.

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

“…Moreover, miR-124 expression was down-regulated in bladder cancer tissues compared with corresponding adjacent non-tumor tissues which were consistent with previous report [53]. In bladder cancer tissues, miR-124 expression was inversely correlated with XIST and AR expression, respectively.…”

“…According to previous studies, miR-124 plays a suppressive role in cancers [20]. The role of miR-124 in bladder cancer was reported [21]. Here, we hypothesized that XIST might act as a ceRNA to sponge miR-124, thus to regulate AR expression.…”

“…In this study, we focused on miR-124 because of its potential suppressive function in human malignances, including bladder cancer. Wang et al indicated that miR-124 exerts tumor suppressive functions on the cell proliferation, motility and angiogenesis of bladder cancer by fine-tuning UHRF1 [21]. Zhang and colleagues reported that miR-124 retards bladder cancer growth by directly targeting CDK4 [46].…”

Vasculogenic mimicry in bladder cancer and its association with the aberrant expression of ZEB1

“…Wang et al (25) found that human bladder transitional cancer cell lines J82 and T24 generated VM formation, and this was inhibited by downregulation of UHRF1 via miR-124. Likewise, in the current study, we confirmed that bladder transitional cancer cell lines UM-UC-3 and J82 can generate VM structures in a 3-D Matrigel culture, but the immortalized human bladder epithelium cell line SV-HUC-1 did not exhibit this ability, even when the seeding concentration was higher or the observation time was longer.…”

Inhibition of MicroRNA-124 Reduces Cardiomyocyte Apoptosis Following Myocardial Infarction via Targeting STAT3

“…MiR-124 is predominantly expressed in normal brain and plays an important role in neural processes from normal neural cell function to the development of central nervous system tumors [24]. Several studies have suggested that miR-124 is significantly downregulated in several human cancers, such as bladder, breast and lung cancer [25][26][27]. Recently, a number of experiments have shown that miR-124 is involved in the regulation of cardiovascular diseases.…”