microRNA‑145 modulates migration and invasion of bladder cancer cells by targeting N‑cadherin

Abstract

MicroRNA (miRNA)‑145 has been demonstrated to serve a role in several types of tumors, however, the potential molecular mechanism of action of miRNA‑145 in bladder cancer metastasis remains to be elucidated. This study aimed to investigate the potential modulation of miRNA‑145 in bladder carcinoma and elucidate the underlying molecular mechanism. The expression of miRNA‑145 in bladder adenocarcinoma tissues and bladder cancer cells was measured by reverse transcription‑quantitative polymerase chain reaction. miRNA‑145 mimics and inhibitor were transfected into bladder cancer (BC) cells to determine the role of miRNA‑145 on cell motility and invasion measured by wound healing and transwell assays. Luciferase assay was performed to confirm whether N‑cadherin was the direct target of miRNA‑145. Subsequently, expression of N‑cadherin and matrix metalloproteinase‑9 (MMP9) in BC cells were detected by western blot analysis. miRNA‑145 was significantly downregulated cells and tissues from patients with BC, compared with healthy controls. miRNA‑145 markedly inhibited the ability of BC cells to migrate and invade. Furthermore, N‑cadherin was identified as a target of miRNA‑145 in BC cells. MMP9, acting downstream of N‑cadherin, was downregulated in BC cells by miRNA‑145. In the present study, miRNA‑145 suppressed the migration and invasion of BC cells by regulating N‑cadherin. The results of the present study indicated that miRNA‑145 may function as a tumor suppressor and may have a potential to be a diagnostic and predictive biomarker, and a therapeutic target for treatment of BC.

Expression Profile of Micrornas (106b-3p, 130b-3, 145-3p and 199a-5p) in Urine and Serum Samples From Patients With the Diagnosis of Bladder Cancer

“…Studies have shown a reduced level of this miRNA in cells and tissues of patients with bladder cancer as compared to the control group. [38] Similar observations were noted in our study, however, on other biological material. We also found that the relative expression levels of miRNA 145-3p in urine of patients suffering from BCa was reduced.…”

The Microrna-143/145 Cluster in Tumors: A Matter of Where and When

“…In prostate cancer, ZEB2 was shown to be involved in a double negative feedback loop with miR-145 [81], and indeed ZEB2 and miR-145 levels are negatively correlated in prostate cancers. Moreover, miR-145 overexpression in DU145 prostate cancer cells could downregulate the mesenchymal markers N-CADHERIN, VIMENTIN and FIBRONECTIN while increasing E-CADHERIN levels [81,82]. Similar results were obtained in PC3 prostate cancer cells by Peng and colleagues, who showed that miR-143 and -145 levels were lower in samples from bone metastatic lesions that in primary prostate cancers, suggesting that their downregulation might help cells to undergo EMT and escape from the primary site [83].…”

MicroRNA-145 suppresses epithelial to mesenchymal transition in pancreatic cancer cells by inhibiting TGF-β signaling pathway

“…The dysregulation of miRNA-145 expression has been reported in different types of cancers. In bladder cancer and lung cancer, miRNA-145 inhibits migration and invasion of tumor cells by directly targeting N-cadherin [12,13]. In the present study, we found that the expression of miRNA-145 was down-regulated in PC tissues comparing to the paired adjacent no cancerous tissues.…”

“…Studies showed that miR-145 was capable of binding to the 3'-UTR of SMAD3, thereby inhibiting its protein expression and subsequent inhibiting the transforming growth factor beta (TGF-β)-induced epithelial to mesenchymal transition (EMT) [10,11]. However, miR-145 could promote the EMT in human peritoneal mesothelial cells by restraining the fibroblast growth factor 10 [12]. The mechanism of miR-145 needs to be elucidated in the EMT process.…”

“…For instance, TGF-β triggered EMT by reducing epithelial biomarkers such as E-cadherin and accumulating of mesenchymal biomarkers such as vimentin [15,16]. Some studies had demonstrated that miR-145 can suppress TGF-β induced EMT and attenuate cell migration and invasion [12]. However, the association between miRNA-145 and TGF-β-induced EMT remains unclear in pancreatic cancer.…”