MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene

Abstract

has been reported to be overexpressed in many types of cancers, but its role in bladder cancer has not been elucidated yet. Here, we report that miR-139-5p functions as a tumor suppressor in bladder cancer and inhibits the cancer stem cell self-renewal by targeting Bmi1 directly. We found that miR-139-5p expression was significantly downregulated in the bladder cancer specimens compared with that in adjacent normal tissues. In vitro, restoration of miR-139-5p expression significantly inhibited the proliferation of bladder cancer cells. Mechanism analysis revealed that miR-139-5p could decrease Bmi1 protein levels by binding to the 3′ untranslated region of Bmi1 messenger RNA. Stem cell-related proteins such as c-MYC, NANOG, OCT4, and KLF4 and signaling pathways such as Wnt signaling were suppressed by restoration of miR-139-5p in bladder cancer cells. In addition, miR-139-5p expression also blocked selfrenewal of bladder cancer stem cells by inhibiting Bmi1. In summary, our study supports that miR-139-5p acts as a tumor suppressor in bladder cancer development and suppresses cancer stem cell property of bladder cancer. Our study also suggests that miR-139-5p has the potential to be used as a therapeutic molecule for bladder cancer treatment.

MicroRNA‐139 is a predictor of prostate cancer recurrence and inhibits growth and migration of prostate cancer cells through cell cycle arrest and targeting IGF1R and AXL

“…Previous studies have shown that miR‐139‐5p decreases cancer cell growth in many different types of cancers . Similarly, our data show decreased proliferation and migration in PC3 and Du145 PCa cell lines overexpressing miR‐139 compared with control cells (Figures and ).…”

“…AXL also activates the PI3K/AKT cascade . AKT activation leads to cyclin D1 upregulation through inhibition of GSK3β . Cyclin D1 then stimulates cell cycle entry and proliferation .…”

Sodium butyrate inhibits migration and induces AMPK‐mTOR pathway‐dependent autophagy and ROS‐mediated apoptosis via the miR‐139‐5p/Bmi‐1 axis in human bladder cancer cells

“…The key roles of Bmi‐1 in cell migration, autophagy, ATP production, and ROS generation have been reported in several studies . Thus, we expected that NaB would modulate migration, autophagy, ATP production, and ROS generation through the miR‐139‐5p/Bmi‐1 axis in human bladder cancer cells.…”

“…Upregulated miR-139-5p leads to tumor invasion and growth inhibition. 43 A previous study reported that miR-139-5p inhibits bladder cancer proliferation and self-renewal by targeting Bmi-1 directly, 18 which indicates that miR-139-5p might play an important role in human bladder cancer. Since Bmi-1 is a direct target of miR-139-5p, we also determined the mRNA and protein expression levels of Bmi-1, and the results confirmed that NaB treatment upregulated miR-139-5p and depleted Bmi-1 at the mRNA and protein levels in T24 and 5637 cells ( Figure 2C,D).…”

“…16,17 In addition, miR-139-5p has been reported to be downregulated in bladder cancer and exerts antitumor effects by directly targeting Bmi-1. 18 The epithelial-mesenchymal transition (EMT) is a vital process in cancer metastasis and is attracting increasing attention in basic research on cancer therapies. 19 Interestingly, Bmi-1 has been reported to be an important target of microRNAs that is closely relate to the reversal of EMT processes.…”