Exosomal miR-93-5p as an important driver of bladder cancer progression

Abstract

Background: Tumor-derived exosomes are involved in the process of tumor metastasis and angiogenesis.MicroRNAs (miRNAs) are the most widely investigated factors in exosomes. Therefore, we hope to find a new therapeutic target in bladder cancer (BLCA), which has high incidence rate and mortality. Methods: Exosomal microRNA(miR)-93-5p expression level, downstream target molecules, and biological functions were examined with bioinformatics technology. Exosomes were extracted by sequential differential centrifugation and verified by transmission electron microscopy. The exosomal miR-93-5p on cell proliferation, invasion, and angiogenesis abilities in 5637 and T24 cells was determined by Cell Counting Kit 8 (CCK-8), colony-forming assay, Transwell assay, and vascular ring formation assay. A mouse xenograft model with intratumor injection was adopted to evaluate the correlation between BLCA-derived exosomes and tumor growth in vivo. Results:The results revealed that exosomes play an important role in the biological progression of BLCA, with miR-93-5p being a particularly important molecule. Compared to normal cells, more malignant cells release more exosomal miR-93-5p, and tumor-derived exosomal miR-93-5p could significantly promote cell proliferation, invasion, and angiogenesis in vitro and in vivo. We identified phosphatase and tensin homolog (PTEN) as the most significant target of miR-93-5p in BLCA and human umbilical vein endothelial cells.Conclusions: Our study successfully revealed the biological role and mechanism of BLCA-derived exosomes in tumor progression. Target at tumor exosomes and exosomal miR-93-5p may be an effective treatment in BLCA.

The value of urinary exosomal microRNA‐21 in the early diagnosis and prognosis of bladder cancer

“…Several miNRAs closely associated with BC progression, including miR‐146a‐5p, 10 miR‐93‐5p, 11 miR‐663b, 12 miR‐21, and miR‐4454, 13 were selected as candidate miRNAs for BC diagnosis due to their reported high expression in BC tissues and involvement in intercellular communication via the exosomal pathway in the tumor microenvironment. RT‐qPCR analysis revealed significantly higher relative expression levels of miR‐146a‐5p (0.13 [0.04, 0.43]), miR‐93‐5p (0.19 [0.02, 0.75]), miR‐663b (0.11 [0.03, 0.44]), miR‐21 (0.32 [0.06, 1.65]), and miR‐4454 (0.35 [0.02, 1.80]) in urinary exosomes of the BC group compared to miR‐146a‐5p (0.08 [0.03, 0.24]), miR‐93‐5p (0.13 [0.04, 0.46]), miR‐663b (0.09 [0.04, 0.22]), miR‐21 (0.12 [0.04, 0.36]), and miR‐4454 (0.15 [0.04, 0.76]) in the control group (Figure 2A–E, all p < 0.0001).…”

“…Several miNRAs closely associated with BC progression, including miR-146a-5p, 10 miR-93-5p, 11 miR-663b, 12 miR-21, and miR-4454, 13 were selected as candidate miRNAs for BC diagnosis due to their reported high expression in BC tissues and involvement in intercellular…”

“…Notably, exosomal miR‐21 secreted by BC cells has been shown to activate the PI3K/AKT pathway in macrophages, thereby fostering cancer progression 9 . In our quest for a reliable urinary exosomal miR serving as a diagnostic and prognostic marker for BC, we conducted a thorough literature review, identifying five miRNAs associated with BC progression: miR‐146a‐5p, 10 miR‐93‐5p, 11 miR‐663b, 12 miR‐21, and miR‐4454 13 . These miRNAs are known to participate in intercellular communication within tumor microenvironment via the exosomal pathway, prompting speculation about their potential high detection rates in urinary exosomes and their candidacy as diagnostic markers for BC.…”

Tumor-derived exosomal miR-1247-3p promotes angiogenesis in bladder cancer by targeting FOXO1

“…Tumor-derived exosomes participate in the progression of angiogenesis in bladder cancer. 21 miRNA is the most extensively studied factor in exosomes. Hence, it is necessary to explore a novel therapeutic target in bladder cancer, which is a disease with high mortality rate and serious impact on people’s lives.…”

Characterization of a miRNA Signature with Enhanced Diagnostic and Prognostic Power for Patients with Bladder Carcinoma

“…hsa-mir-93 has been associated with poor prognosis in pancreatic cancer [43] and is reported to target LATS2, which encodes for a tumor suppressor kinase, ultimately enhancing metastasis [44]. Its presence in exosomes from bladder cancer patients has been reported as an important determinant for the progression of the disease [45]. Finally, hsa-mir-130b also promotes the proliferation of bladder cancer cells via targeting of VGLL4 [46].…”