MicroRNAs: Key Players in Bladder Cancer

Li, Qi; Wang, Helei; Peng, Hourong; Huang, Qiyu; Huyan, Ting; Huang, Qingsheng; Yang, Hui; Shi, Junling

doi:10.1007/s40291-019-00410-4

Cited by 38 publications

(23 citation statements)

References 195 publications

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“…There are decreased Ki67 positive cells in miR-375-3p agomir group compared with NC agomir group altered miRNA profile of the tumor, which indicates the exosomal miRNAs can be identified as potential circulating tumor markers. 34,37 Over 200 miRNAs or miRNA families/clusters have been recognized as aberrantly expressed between BC patients and healthy controls or between MIBC and NMIBC patients, 38 and many miRNAs have been recognized as significantly dysregulated in BC exosomes. In a study by Baumgart et al, a panel of miRNAs (miR-141-3p, miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-205-5p, miR-224-5p, and miR-429-3p) was found to be downregulated in exosomes of invasive BC cells (T24, J82, and 253J-BV) compared to noninvasive BC cells (RT112; 5637), while miR-99a-5p and miR-137-3p were increasingly expressed in invasive BC cells.…”

Section: Discussionmentioning

confidence: 99%

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

Huyan

Cai

et al. 2020

FASEB j.

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miR‐375‐3p is a significantly downregulated miRNA in bladder cancer (BC). However, its role in BC regulation is still unclear. In this study, we reported that miR‐375‐3p overexpression inhibited proliferation and migration and promoted apoptosis in BC cells. Frizzled‐8 (FZD8) gene is identified as the direct miR‐375‐3p targeting gene. miR‐375‐3p blocks the Wnt/β‐catenin pathway and downstream molecules Cyclin D1 and c‐Myc by inhibiting the expression of FZD8 directly, it could increase caspase 1 and caspase 3 expression and promote T24 cell apoptosis as well. miR‐375‐3p also showed a significant inhibitory effect in vivo in bladder tumor‐bearing nude mice, as demonstrated by the reduced tumor volume and Ki67 proliferation index in tumor tissue. Collectively, miR‐375‐3p is a suppressor of BC that inhibits proliferation and metastasis, and promotes apoptosis in BC cells as well as suppresses tumor growth in a T24 xenograft mouse model, which could be used as a potential therapeutic approach for BC in future.

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Section: Discussionmentioning

confidence: 99%

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

Huyan

Cai

et al. 2020

FASEB j.

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“…Increasing evidences have found that miRNAs are an attractive biomarker source for cancer research as their high stability . Up to now, lots of miRNAs have been reported to be deregulated in bladder cancer and involved in cancer progression . For instance, miR‐153 expressed at a low level in bladder cancer tissues and cells as compared with the normal tissues and cells, and low expression of miR‐153 was closely associated with advanced tumor stage and poor overall survival .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐769‐5p suppresses cell growth and migration via targeting NUSAP1 in bladder cancer

Chen

Zhang

Kadier

et al. 2020

Clinical Laboratory Analysis

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Background Nucleolar and spindle‐associated protein 1 (NUSAP1) has been identified to be strongly implicated in the carcinogenesis of cervical carcinoma, breast cancer, and liver cancer, and shows a high expression level in bladder cancer, indicating that NUSAP1 might be a potent target for cancer treatment. Using bioinformatics methods, we found that NUSAP1 was a putative target of miR‐769‐5p. Here, we aimed to explore whether miR‐769‐5p is involved in bladder cancer progression via targeting NUSAP1. Methods MiR‐769‐5p expression patterns in bladder cancer tissues and cells were detected by RT‐PCR. Kaplan‐Meier was used to determine the clinical effects of miR‐769‐5p expression levels on the overall survival of bladder cancer patients. Bioinformatics methods were used to predict the binding sites between miR‐769‐5p and NUSAP1, which was verified by the luciferase gene reporter assay. CCK‐8, flow cytometry, wound healing and transwell chamber experiments were performed to test cell growth, apoptosis, migration and invasion capacities. Results miR‐769‐5p was lowly expressed in bladder cancer tissues and cells, which was closely associated with poor prognosis. Overexpression of miR‐769‐5p induced significant repressions in cell growth, migration, and invasion and caused an obvious increase in cell apoptosis, whereas these tendencies were reversed when NUSAP1 was upregulated. Conclusion This study demonstrates that miR‐769‐5p functions as a tumor suppressor in bladder cancer via targeting NUSAP1.

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“…MicroRNAs (miRNAs), a class of small non-coding RNAs, have important roles in the regulation of genes involved in bladder cancer development, progression, and metastasis. Many miRNAs have been studied as potential noninvasive tumor markers, but the diagnostic specificity of miRNAs detection remains to be improved in bladder cancers [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Genomic Instability Signature of Palindromic Non-Coding Somatic Mutations in Bladder Cancer

Vacher

Suybeng

Girard

et al. 2020

Cancers

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Numerous pan-genomic studies identified alterations in protein-coding genes and signaling pathways involved in bladder carcinogenesis, while non-coding somatic alterations remain weakly explored. The goal of this study was to identify clinical biomarkers in non-coding regions for bladder cancer patients. We have previously identified in bladder tumors two non-coding mutational hotspots occurring at high frequencies (≥30%). These mutations are located close to the GPR126 and PLEKHS1 genes, at the guanine or the cytosine of a TGAACA core motif flanked, on both sides, by a stretch of palindromic sequences. Here, we hypothesize that such a pattern of recurrent non-coding mutations could be a signature of somatic genomic instability specifically involved in bladder cancer. We analyzed 26 additional mutable non-coding sites with the same core motif in a cohort of 103 bladder cancers composed of 44 NMIBC cases and 59 MIBC cases using high-resolution melting (HRM) and Sanger sequencing. Five bladder cancers were additionally analyzed for protein-coding gene mutations using a targeted NGS panel composed of 571 genes. Expression levels of three members of the APOBEC3 family genes were assessed using real-time quantitative RT-PCR. Non-coding somatic mutations were observed for at least one TGAACA core motif locus in 62.1% (64/103) of bladder tumor samples. These non-coding mutations co-occurred in the bladder tumors but were absent in prostate tumor, HPV-positive Head and Neck Squamous Cell Carcinoma, and high microsatellite instability (MSI-H) colorectal tumor series. This signature of palindromic non-coding somatic mutations, specific to bladder tumors, was not associated with patients’ outcome and was more frequent in females. Interestingly, this signature was associated with high tumor mutational burden (TMB) and high expression levels of APOBEC3B and interferon inducible genes. We identified a new type of somatic genomic instability targeting the TGAACA core motif loci flanked by palindromic sequences in bladder cancer. This mutational signature is a promising candidate clinical biomarker for the early detection of relapse and a major low-cost alternative to the TMB to monitor the response to immunotherapy for bladder cancer patients.

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MicroRNAs: Key Players in Bladder Cancer

Cited by 38 publications

References 195 publications

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

MicroRNA‐769‐5p suppresses cell growth and migration via targeting NUSAP1 in bladder cancer

Genomic Instability Signature of Palindromic Non-Coding Somatic Mutations in Bladder Cancer

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