Transcriptional downregulation of miR‐127‐3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5

Fan, Jiaxing; Du, Wei; Zhang, Hui; Wang, Yunchao; Li, Kai; Meng, Yong Hong; Wang, Jianning

doi:10.1002/1873-3468.13624

Cited by 26 publications

(25 citation statements)

References 39 publications

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“…Moreover, the proteasome may be involved in the development of cancer metastasis (53,54). Fan et al reported that miR-127-3p could target PSMB5 to inhibit the invasion and migration of PCa cells (53). Consistent with our results, several studies found that the proteasome can be detected in exosomes (42,55,56).…”

Section: Discussionsupporting

confidence: 91%

Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer

et al. 2020

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Background: Clinical management of metastatic gastric cancer (mGC) remains a major challenge due to a lack of specific biomarkers and effective therapeutic targets. Recently, accumulating evidence has suggested that exosomes play an essential role in cancer metastasis and can be an excellent reservoir of novel biomarkers and candidate therapeutic targets for cancer. Therefore, in this study, we aimed to reveal the proteomic profile of mGC-derived exosomes. Methods: Exosomes were isolated from pooled serum samples of 20 mGC patients and 40 healthy controls (HC) by ultracentrifugation. Next, quantitative proteomic analyses were applied to analyze the protein profiles of the exosomes, and bioinformatic analyses were conducted on the proteomic data. Finally, the expression of exosomal protein candidates was selectively validated in individual subjects by western blot analysis. Results: We isolated exosomes from serum samples. The size of the serum derived exosomes ranged from 30 to 150 nm in diameter. The exosomal markers CD9 and CD81 were observed in the serum exosomes. However, the exosomal negative marker calnexin, an endoplasmic reticulum protein, was not detected in exosomes. Overall, 443 exosomal proteins, including 110 differentially expressed proteins (DEPs) were identified by quantitative proteomics analyses. The bioinformatics analyses indicated that the upregulated proteins were enriched in the process of protein metabolic, whereas the downregulated proteins were largely involved in cell-cell adhesion organization. Surprisingly, 10 highly vital proteins (UBA52,

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Section: Discussionsupporting

confidence: 91%

Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer

et al. 2020

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“…All those miRNAs exhibited high discriminatory power (AUC above 0.85). MiR-127-3p has been shown to exhibit a tumor suppressor function in osteosarcoma [52], giant cell tumors of bone [53], prostate cancer bone metastasis [54], epithelial ovarian cancer [55], and glioblastoma [56]. miR-409-3p inhibits cell proliferation and invasion of osteosarcoma [57], tongue squamous cell carcinoma [58], breast cancer [59], and prostate cancer [60].…”

Section: Discussionmentioning

confidence: 99%

“…Ion AmpliSeq Comprehensive Cancer Panel (ThermoFisher Scientific, Waltham, MA, United States) libraries were prepared from DNA samples for the analysis of the coding regions of 409 oncogenes and tumor suppressor genes by sequencing on an Ion Proton sequencer with the Ion PI Hi-Q Chef Kit, loading four samples onto an Ion PI Chip, as described previously [54].…”

Section: Profiling Of Dna Variantsmentioning

confidence: 99%

Differences between Well-Differentiated Neuroendocrine Tumors and Ductal Adenocarcinomas of the Pancreas Assessed by Multi-Omics Profiling

Starzyńska

Karczmarski

Paziewska

et al. 2020

IJMS

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Most pancreatic neuroendocrine tumors (PNETs) are indolent, while pancreatic ductal adenocarcinomas (PDACs) are particularly aggressive. To elucidate the basis for this difference and to establish the biomarkers, by using the deep sequencing, we analyzed somatic variants across coding regions of 409 cancer genes and measured mRNA/miRNA expression in nine PNETs, eight PDACs, and four intestinal neuroendocrine tumors (INETs). There were 153 unique somatic variants considered pathogenic or likely pathogenic, found in 50, 57, and 24 genes in PDACs, PNETs, and INETs, respectively. Ten and 11 genes contained a pathogenic mutation in at least one sample of all tumor types and in PDACs and PNETs, respectively, while 28, 34, and 11 genes were found to be mutated exclusively in PDACs, PNETs, and INETs, respectively. The mRNA and miRNA transcriptomes of PDACs and NETs were distinct: from 54 to 1659 differentially expressed mRNAs and from 117 to 250 differentially expressed miRNAs exhibited high discrimination ability and resulted in models with an area under the receiver operating characteristics curve (AUC-ROC) >0.9 for both miRNA and mRNA. Given the miRNAs high stability, we proposed exploring that class of RNA as new pancreatic tumor biomarkers.

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“…Siu et al demonstrated that KLF4 functions as a transcription factor to activate the AR-miR-1 signaling pathway to constrain the tumor-suppressive role of miR-1 [50]. CTCF, a downstream transcription activator of Smad and Myc signaling, contributes to slowing down metastasis in PCa through directly interacting with the miR-127-3p promoter, in which the downregulation of miR-127-3p accompanies proteasome subunit beta type-5 (PSMB5) elevation and subsequently leads to the activation of BM [55][56][57]. All of the above research draws a large picture of the regulatory mechanism of BM in PCa cells, and Figure 1 summarizes these signaling cascades.…”

Section: Other Minor Emt Contributorsmentioning

confidence: 99%

Ras and Wnt Interaction Contribute in Prostate Cancer Bone Metastasis

2020

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Prostate cancer (PCa) is one of the most prevalent and malignant cancer types in men, which causes more than three-hundred thousand cancer death each year. At late stage of PCa progression, bone marrow is the most often metastatic site that constitutes almost 70% of metastatic cases of the PCa population. However, the characteristic for the osteo-philic property of PCa is still puzzling. Recent studies reported that the Wnt and Ras signaling pathways are pivotal in bone metastasis and that take parts in different cytological changes, but their crosstalk is not well studied. In this review, we focused on interactions between the Wnt and Ras signaling pathways during each stage of bone metastasis and present the fate of those interactions. This review contributes insights that can guide other researchers by unveiling more details with regard to bone metastasis and might also help in finding potential therapeutic regimens for preventing PCa bone metastasis.

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Transcriptional downregulation of miR‐127‐3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5

Cited by 26 publications

References 39 publications

Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer

Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer

Differences between Well-Differentiated Neuroendocrine Tumors and Ductal Adenocarcinomas of the Pancreas Assessed by Multi-Omics Profiling

Ras and Wnt Interaction Contribute in Prostate Cancer Bone Metastasis

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