Regulatory functions of miR‑200b‑3p in tumor development (Review)

Chen, Sheng; Tu, Yifeng; Yuan, Hang; Shi, Zhan; Guo, Yang; Gong, Wenjing; Tu, Shiliang

doi:10.3892/or.2022.8307

Cited by 12 publications

(4 citation statements)

References 59 publications

(94 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data indicate that miR-200b was upregulated in pathological ECs vs. healthy endothelium upon normoxia. As some studies have indicated, miR-200b silences angiogenesis and is correlated with the metastatic cascade in breast tumor, and we present that mir-200b-3p is also deregulated in endothelial cells derived from this pathological tissue ( Amorim et al, 2019 ; Chen et al, 2022 ) The bioinformatics analysis shows that VEGFA and KDR1 (VEGFA receptor) may be mir-200b-3p target genes. In our model, this effect was not observed at the transcript level as both miR-200b that is high in cancer tissue–derived endothelial cells and miR mimic-treated healthy cells were characterized by VEGF mRNA.…”

Section: Discussionmentioning

confidence: 63%

Microenvironment commits breast tumor ECs to dedifferentiation by micro-RNA-200-b-3p regulation and extracellular matrix remodeling

Wilkus-Adamczyk,

Brodaczewska,

Majewska

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Introduction: Hypoxia shapes the tumor microenvironment, modulates distinct cell population activities, and activates pathological angiogenesis in cancer, where endothelial cells (ECs) are the most important players. This study aimed to evidence the influences of the tumor microenvironment on the global gene expression pattern characteristic for ECs and the distinct responses displayed by tumor-derived ECs in comparison to the healthy endothelium during endothelial to mesenchymal transition (EndMT) and its regulation by miR-200-b-3p.Methodology: Immortalized lines of ECs from the same patient with breast cancer, healthy breast tissue (HBH.MEC), and primary tumor (HBCa.MEC) were used. The experiments were performed in normoxia and hypoxia for 48 h. By using the wound healing test, we investigated the migration abilities of ECs. Global gene expression analysis with NGS was carried out to detect new pathways altered in pathological ECs and find the most changed miRNAs. The validation of NGS data from RNA and miRNA was estimated by qPCRs. Mimic miR-200b-3p was used in HBH.MEC, and the targets VEGF, Bcl2, ROCK2, and SP1 were checked.Results: Hypoxia influences EC migration properties in wound healing assays. In hypoxia, healthy ECs migrate slower than they do in normoxia, as opposed to HBCa.MEC, where no decreased migration ability is induced by hypoxia due to EndMT features. NGS data identified this process to be altered in cancer ECs through extracellular matrix (ECM) organization. The deregulated genes, validated by qPCR, included SPP1, ITGB6, COL4A4, ADAMST2, LAMA1, GAS6, PECAM1, ELN, FBLN2, COL6A3, and COL9A3. NGS also identified collagens, laminins, fibronectins, and integrins, as being deregulated in tumor-derived ECs. Moreover, the analysis of the 10 most intensively modified miRNAs, when breast tumor–derived ECs were compared to healthy ECs, shed light on miR-200b-3p, which is strongly upregulated in HBCa.MECs when compared to HBH.MECs.Discussion and conclusion: The pathological ECs differed significantly, both phenotypically and functionally, from the normal corresponding tissue, thus influencing their microenvironment cross-talk. The gene expression profile confirms the EndMT phenotype of tumor-derived ECs and migratory properties acquisition. Moreover, it indicates the role of miR-200b-3p, that is, regulating EndMT in pathological ECs and silencing several angiogenic growth factors and their receptors by directly targeting their mRNA transcripts.

show abstract

Section: Discussionmentioning

confidence: 63%

Microenvironment commits breast tumor ECs to dedifferentiation by micro-RNA-200-b-3p regulation and extracellular matrix remodeling

Wilkus-Adamczyk,

Brodaczewska,

Majewska

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…miR-200-3p targets a multitude of genes and, similarly to miR-31 and miR-125b, miR-200b-3p is reported to have both anti-tumorigenic and pro-tumorigenic activities [35]. While miR-200b-3p appears to have anti-tumorigenic activity in most tissues, high expression of miR-200b is associated with ovarian cancer progression and increased tumor stage [36,37]. This suggests that in endometriosis tissue, miR-200b-3p may be associated with pro-tumorigenic pathways.…”

Section: Discussionmentioning

confidence: 99%

miR 31-3p Has the Highest Expression in Cesarean Scar Endometriosis

Szubert

Nowak-Glück

Domańska-Senderowska

et al. 2022

IJMS

View full text Add to dashboard Cite

Micro-RNAs expression can vary between different forms of endometriosis, but data on miRNA expression in cesarean scar endometriosis is lacking. The present study is comprised of 30 patients with endometriosis in the cesarean scar (scar endometriosis, SE), 14 patients with deep infiltrating endometriosis (DIE), 47 patients with endometrioma (ovarian endometrial cyst, OE), and 33 patients with healthy ovarian tissue as the control group (CG). In the initial experiment to identify possible dysregulated miRNAs, the levels of 754 miRNAs in formalin-fixed paraffin-embedded tissue (FFPE) samples from OE, high-grade ovarian cancer, endometrioid ovarian cancer, and CG were measured. We identified seven potentially dysregulated miRNAs: miR-1-3p, miR-31-3p, miR-125b-1-3p, miR-200b-3p, miR-548d, miR-502, and miR-503. We then examined the expression profiles of each of these miRNAs individually in the SE, DIE, OE, and CG FFPE samples using RT-qPCR. miR-31-3p had significantly higher levels of expression and miR-125b-1-3p had significantly lower levels of expression in SE compared to the controls. Overall, the higher expression levels of miR-31-3p and the lower expression levels of miR-125b-1-3p are consistent with the benign nature of SE. Importantly, the results of the present study demonstrate the possibility of using miRNA to monitor the risk of malignant transformation of endometriosis tissue.

show abstract

“…It is possible that during the early stages of carcinogenesis, upregulation of miR-200b has a role in proliferation by inhibiting CDKN1B , while later, during the progression of CRC from pT3 to pT4a, downregulation of miR-200b promotes invasiveness and migration, i.e., serosal membrane invasion by targeting other yet unidentified genes. It has been shown that in addition to EMT, miR-200b can also regulate tumour proliferation, apoptosis, invasion, migration and chemotherapy resistance through the WNT/β-catenin pathway, MAPK signalling pathway, PI3K/Akt pathway and others [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

miR-200b, ZEB2 and PTPN13 Are Downregulated in Colorectal Carcinoma with Serosal Invasion

et al. 2022

View full text Add to dashboard Cite

Serosal invasion is an independent negative prognostic factor in certain cancers, including CRC. However, the mechanisms behind serosal invasion are poorly understood. We therefore assumed that epithelial-mesenchymal transition (EMT) might be involved. Our study included 34 patients with CRC, 3 stage pT2, 14 stage pT3 and 17 showing serosal invasion (stage pT4a according to TNM staging system). RNA isolated from formalin-fixed paraffin-embedded tissue samples was analysed for expression of the miR-200 family and their target genes CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2 and ZEB2 using real-time PCR. We found upregulation of miR-200b and ONECUT2 in CRC pT3 and pT4a compared to normal mucosa, and downregulation of CDKN1B in CRC pT3. Moreover, we observed, downregulation of miR-200b, PTPN13 and ZEB2 in CRC with serosal invasion (pT4a) compared to pT3. Our results suggest the involvement of partial EMT in serosal invasion of CRC. In addition, PTPN13 seems to be one of the important regulators involved in serosal invasion, and ONECUT2 in tumour growth.

show abstract

Regulatory functions of miR‑200b‑3p in tumor development (Review)

Cited by 12 publications

References 59 publications

Microenvironment commits breast tumor ECs to dedifferentiation by micro-RNA-200-b-3p regulation and extracellular matrix remodeling

Microenvironment commits breast tumor ECs to dedifferentiation by micro-RNA-200-b-3p regulation and extracellular matrix remodeling

miR 31-3p Has the Highest Expression in Cesarean Scar Endometriosis

miR-200b, ZEB2 and PTPN13 Are Downregulated in Colorectal Carcinoma with Serosal Invasion

Contact Info

Product

Resources

About