Expression of bone morphogenetic protein-2 and -7 in urinary bladder cancer predicts time to tumor recurrence

Kuzaka, B; Janiak, Marek; Włodarski, K; Radziszewski, Piotr; Włodarski, Paweł

doi:10.5114/aoms.2014.46796

Cited by 11 publications

(8 citation statements)

References 33 publications

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“…In this study, we found that BMP9 could promote the proliferation and migration of bladder cancer cells. This effect is consistent with its family member BMP2 and BMP7 [ 20 ]. Since a number of studies have reported that lncRNA （long non-coding RNA） is implicated in the development of bladder cancer [ 21 , 22 , 23 ], we intended to explore whether BMP9 could promote the proliferation and migration of cancer cells through lncRNAs.…”

Section: Introductionsupporting

confidence: 85%

BMP9 Promotes the Proliferation and Migration of Bladder Cancer Cells through Up-Regulating lncRNA UCA1

Gou

Liu

Xia

et al. 2018

IJMS

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As the most common malignant tumor of the urinary system worldwide, the bladder tumor has a high mortality rate, which is mainly due to its onset of concealment. Therefore, research into novel diagnostic markers and treatment of bladder cancer is urgently needed. BMP9 (Bone morphogenetic protein 9) is a member of BMP, which belongs to the TGF-β (transforming growth factor-β) superfamily. It has been associated with multiple tumors. We found that BMP9 is highly expressed in bladder cancer cells and it could significantly promote the proliferation and migration of bladder cancer cells. In the study of the mechanism of this effect, we found that BMP9 can increase the expression of lncRNA UCA1 (Urothelial cancer associated 1) through phosphorylated AKT. The promoting effect of BMP9 on bladder cancer cells was rescued after interfering with UCA1 in BMP9 overexpressed bladder cancer cells both in vitro and in vivo. Our research confirms that BMP9 promotes the proliferation and migration of bladder cancer cells through up-regulated lncRNA UCA1. It also shows that BMP9 is a novel diagnostic marker and a potential therapeutic target in bladder cancer.

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Section: Introductionsupporting

confidence: 85%

BMP9 Promotes the Proliferation and Migration of Bladder Cancer Cells through Up-Regulating lncRNA UCA1

Gou

Liu

Xia

et al. 2018

IJMS

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“…Interestingly, the functional target genes of miR-106b-5p were enriched in the bone morphogenetic protein (BMP) pathways. The BMP pathway has been shown to associate with bladder cancer invasiveness and tumor recurrence [ 22 , 23 ]. McConkey et al [ 24 ] shows bone metastasis occurs disproportionately in p53-like bladder cancer.…”

Section: Resultsmentioning

confidence: 99%

Identification of microR-106b as a prognostic biomarker of p53-like bladder cancers by ActMiR

et al. 2018

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Bladder cancers can be categorized into subtypes according to gene expression patterns. P53-like muscle-invasive bladder cancers are generally resistant to cisplatin-based chemotherapy, but exhibit heterogeneous clinical outcomes with a prognosis intermediate to that of the luminal and basal subtypes. The optimal approach to p53-like tumors remains poorly defined and better means to risk-stratify such tumors and identification of novel therapeutic targets is urgently needed. MicroRNAs (miRNAs) play a key role in cancer, both in tumorigenesis and tumor progression. In the past few years, miRNA expression signatures have been reported as prognostic biomarkers in different tumor types including bladder cancer. However, miRNA’s expression does not always correlate well with its activity. We previously developed ActMiR, a computational method for explicitly inferring miRNA activities. We applied ActMiR to The Cancer Genome Atlas (TCGA) bladder cancer data set and identified the activities of miR-106b-5p and miR-532-3p as potential prognostic markers of the p53-like subtype, and validated them in three independent bladder cancer data sets. Especially, higher miR-106b-5p activity was consistently associated with better survival in these data sets. Furthermore, we experimentally validated causal relationships between miR-106-5p and its predicted target genes in p53-like cell line HT1197. HT1197 cells treated with the miR-106b-5p-specific inhibitor were more invasive while cells treated with the miR-106b-5p-specific mimic were less invasive than corresponding controls. Altogether, our results suggest that miR-106b-5p activity can categorize p53-like bladder tumors into more and less-favorable prognostic groups, which provides critical information for personalizing treatment option for p53-like bladder cancers.

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“…The same results were observed in BMP-7, but not in BMP-4 and -6. Likewise, using real-time polymerase chain reaction, Kuzaka et al (31) have found BMP-2 and BMP-7 downregulation in infiltrating urothelial carcinoma, while BMP-4 was downregulated in non-invasive tumors. Furthermore, they Data are presented as the average (mean ± standard deviation).…”

Section: Discussionmentioning

confidence: 99%

“…Immunostaining score have shown that BMP-2 and BMP-7 correlated with prolonged time to recurrence (31 Also, changes in BMP expression levels in bladder cancer can most likely be related to a significant heterogeneity within the subgroups of TCC (33). Kim et al (12) have also shown that tissue samples from TCC frequently loss expression of BMP receptor and that overexpression of BMP receptor in BMP resistant cell line leads to a restoration of BMP signaling and a decreased rate of tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Bone morphogenic proteins‑2, ‑4, ‑6 and 7 in non‑muscle invasive bladder cancer

et al. 2019

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Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) family and may play an important role in the regulation of malignant cells in bladder cancer. The aim of the present study was to investigate BMP expression in non-muscle invasive bladder cancer. Tumor tissue samples from 71 patients treated with transurethral resection and 10 samples of normal bladder tissue were stained using immunohistochemistry for BMP-2, -4, -6 and -7. The levels of BMP were correlated with the number and size of tumors in the bladder, the pathohistological findings as well as with tumor recurrence and progression. The results of the present study demonstrated that BMP-2 and -7 are highly expressed in normal bladder tissue, but significantly downregulated in cancer samples. This reduction correlates with a faster rate of tumor recurrence as well as with an increase in the number of recurrent tumors. There was no evident interrelation between BMP-2 and -7 reduction and changes in tumor grade and stage. In conclusion, BMP-2 and -7 are potential prognostic factors for tumor recurrence and further studies on BMP and bladder cancer are needed to confirm these results.

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Expression of bone morphogenetic protein-2 and -7 in urinary bladder cancer predicts time to tumor recurrence

Cited by 11 publications

References 33 publications

BMP9 Promotes the Proliferation and Migration of Bladder Cancer Cells through Up-Regulating lncRNA UCA1

BMP9 Promotes the Proliferation and Migration of Bladder Cancer Cells through Up-Regulating lncRNA UCA1

Identification of microR-106b as a prognostic biomarker of p53-like bladder cancers by ActMiR

Bone morphogenic proteins‑2, ‑4, ‑6 and 7 in non‑muscle invasive bladder cancer

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