Exosome–transmitted microRNA‐133b inhibited bladder cancer proliferation by upregulating dual‐specificity protein phosphatase 1

Abstract

Bladder Cancer (BC) is the ninth most common tumor in the world and one of the most common malignant tumors of the urinary system. Some studies reported that miR‐133b expression is reduced in BC, but whether it plays a role in the development of BC and its mechanism is unclear. microRNAs can be packaged into exosomes to mediate communication between tumor cells, affecting their proliferation and apoptosis. The objective of this study was to investigate the effect of exosomal miR‐133b on BC proliferation and its molecular mechanism. Firstly, the expression of miR‐133b was evaluated in BC and adjacent normal tissues, as well as in serum exosomes of BC patients and healthy controls. Then the delivery and internalization of exosomes in cells was observed through fluorescence localization. Cell viability and apoptosis were assessed in BC cells transfected with mimics and incubated with exosomes. The role of exosomal miR‐133b was also analyzed in nude mice transplant tumors. Furthermore, the target gene of miR‐133b was predicted through bioinformatics. The level of miR‐133b was significantly decreased in BC tissues and in exosomes from serum of patients, which was correlated with poor overall survival in TCGA. Exosomal miR‐133b could be obtained using BC cells after transfection with miR‐133b mimics. The miR‐133b expression increased after incubation with exosomal miR‐133b, which lead to the inhibition of viability and increase of apoptosis in BC cells. Exosomal miR‐133b could suppress tumor growth in vivo. In addition, we found that exosomal miR‐133b may play a role in suppressing BC proliferation by upregulating dual‐specificity protein phosphatase 1 (DUSP1). These findings may offer promise for new therapeutic directions of BC.

Nanotechnology in Bladder Cancer: Diagnosis and Treatment

“…In addition, we found that exosomal miR-133b might be involved in inhibiting BC proliferation by rearranging the dual-specific protein phosphatase 1 (DUSP1). These findings could hold new hope for BC treatment directions [ 166 ]. In conclusion, their results provide strong evidence that exosomal miR-133b acts as a tumor inhibitory agent targeting DUSP1 in BC proliferation.…”

“…In addition, exogenous miR-133b can be ingested by BC cells, reducing the malignant phenotype of BC cells. Exosomal miR -133b or other miRNAs better distinguished the disease and make specific advances in the treatment of BC [ 166 ].…”

Extracellular Vesicles as Biomarkers Carriers in Bladder Cancer: Diagnosis, Surveillance, and Treatment

“…Currently, available data regarding exosome utilization in BC treatment are limited. Cai et al examined the effect of exosomal miR-133b on BC cell proliferation both in vitro and in vivo [ 71 ]. The authors isolated exosomes from BC tissue and serum from BC patients, as well as exosomes from BC cell lines (T24 and 5637), reversely transcribed RNA into cDNA and subsequently performed RT-PCR using miR133b specific primer.…”

Emerging Biomarkers for Predicting Bladder Cancer Lymph Node Metastasis

“…Studies have shown that the expression level of miR-133b in BCa tissues is significantly reduced, which was significantly correlated with LNM ( 94 ). MiR-133b may inhibit the proliferation of BCa by up-regulating dual-specificity protein phosphatase 1 (DUSP1) ( 11 ). It inhibited angiogenesis and enhanced BCa cells’ chemosensitivity to Gemcitabine by targeting transgelin 2 (TAGLN2) ( 14 ).…”