Upregulated Wnt-11 and miR-21 Expression Trigger Epithelial Mesenchymal Transition in Aggressive Prostate Cancer Cells

Arısan, Elif Damla; Rencüzoğulları, Özge; Freitas, Ines Lua; Radzali, Syanas; Keskin, Buse; Kothari, Archana; Warford, Antony; Uysal-Onganer, Pinar

doi:10.3390/biology9030052

Cited by 27 publications

(26 citation statements)

References 41 publications

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“…miR-21 has been reported to be upregulated and to promote metastasis in several tumor types [17][18][19][20]. Our previous studies showed that miR-21 is involved in cancer cell invasion and differentiation [21][22][23][24].…”

Section: Introductionmentioning

confidence: 97%

MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells

Arısan

Rencüzoğulları

Cieza-Borrella

et al. 2021

IJMS

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Breast cancer (BCa) is one of the leading health problems among women. Although significant achievements have led to advanced therapeutic success with targeted therapy options, more efforts are required for different subtypes of tumors and according to genomic, transcriptomic, and proteomic alterations. This study underlines the role of microRNA-21 (miR-21) in metastatic MDA-MB-231 breast cancer cells. Following the knockout of miR-21 from MDA-MB-231 cells, which have the highest miR-21 expression levels compared to MCF-7 and SK-BR-3 BCa cells, a decrease in epithelial-mesenchymal transition (EMT) via downregulation of mesenchymal markers was observed. Wnt-11 was a critical target for miR-21, and the Wnt-11 related signaling axis was altered in the stable miR-21 knockout cells. miR-21 expression was associated with a significant increase in mesenchymal markers in MDA-MB-231 BCa cells. Furthermore, the release of extracellular vesicles (EVs) was significantly reduced in the miR-21 KO cells, alongside a significant reduction in relative miR-21 export in EV cargo, compared with control cells. We conclude that miR-21 is a leading factor involved in mesenchymal transition in MDA-MB-231 BCa. Future therapeutic strategies could focus on its role in the treatment of metastatic breast cancer.

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Section: Introductionmentioning

confidence: 97%

MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells

Arısan

Rencüzoğulları

Cieza-Borrella

et al. 2021

IJMS

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“…A number of studies have provided evidence for the therapeutic potential of miRNAs in a wide variety of human cancers, including PCa (30,31). The proposed functional miRNAs exert therapeutic potential by regulating tumor cell biological processes, such as cell proliferation, migration and invasion (32).…”

Section: Discussionmentioning

confidence: 99%

Altered expression of microRNA‑92b‑3p predicts survival outcomes of patients with prostate cancer and functions as an oncogene in tumor progression

et al. 2020

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The global incidence of prostate cancer (PCa) has been increasing in recent years. Meanwhile, some studies have indicated the association between malignancies, such as lung and gastric cancer and PCa, and microRNAs (miRNAs). The present study was designed to assess the prognostic value of miR-92b-3p in patients with PCa and further investigate the biological function of miR-92b-3p. Real-time quantitative polymerase chain reaction was used to estimate the expression of miR-92b-3p in PCa tissues and cell lines compared with normal tissues and cells. Kaplan-Meier method was used to analyze the overall survival rate of patients with PCa. A Cox regression analysis was used to verify the prognostic value of miR-92b-3p. The biological function of miR-92b-3p was investigated using cell experiments. The findings of the present study revealed the upregulated expression of miR-92b-3p in PCa tissues and cells compared with normal tissues and cells. The overexpression of miR-92b-3p was significantly associated with the distant metastasis status and Tumor-Node-Metastasis stage of patients with PCa and predicted poor prognosis of PCa. In addition, the cell experiment results indicated that miR-92b-3p overexpression in PCa cells promoted cell proliferation, migration and invasion. The present study revealed that the overexpression of miR-92b-3p predicted poor prognosis in patients with PCa. Decreased expression of miR-92b-3p can suppress PCa cell proliferation, migration and invasion, which indicated that miR-92b-3p may function as an oncogene and serve as a novel therapeutic target for PCa.

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“…Previously, we had reported that the downregulation of Wnt-11 reduced cell migration and invasion in PCa [36]. We wanted to clarify whether this effect of Wnt-11 was JNK pathway-dependent.…”

Section: Effect Of Silencing Wnt-11 On Cellular Migrationmentioning

confidence: 99%

“…Since we established a link between cell death and JNK signalling, we then wanted to check whether the effect was regulated by Wnt-11. We have previously reported that Wnt-11 is involved in both NED and EMT differentiation in PCa [20,36]; however, how the signals are carried to the downstream target genes are unknown. To test whether the JNK pathway is responsible for Wnt-11 regulated cellular differentiation in PCa, we adopted PC-3 cells as a model, as they express the highest level of Wnt-11 mRNA.…”

Section: Wnt-11 Promotes Emt In Pca Cells Via Jnk Signallingmentioning

confidence: 99%

Inhibition on JNK Mimics Silencing of Wnt-11 Mediated Cellular Response in Androgen-Independent Prostate Cancer Cells

Arısan

Rencüzoğulları

Keskin

et al. 2020

Biology

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Prostate cancer (PCa) is one of the most common cancers among men, and one of the leading causes of cancer death for men. The c-Jun N-terminal kinase (JNK) pathway is required for several cellular functions, such as survival, proliferation, differentiation, and migration. Wnt-11, a member of the Wnt family, has been identified for its upregulation in PCa; however, downstream signalling of Wnt-11 remains to be fully characterized. In this study, we investigated the role of the JNK pathway as a potential downstream factor for Wnt-11 signalling. For this purpose, LNCaP, DU145, and PC-3 PCa cells and normal epithelial PNT1A cells were treated with a specific JNK kinase inhibitor: JNKVIII. Our results showed that JNK inhibition decreased mitochondrial membrane potential and promoted cell death in a cell type-dependent manner. We found that JNK inhibition led to an increase in autophagy and prevented epithelial–mesenchymal transition (EMT) in independently growing androgen cells. JNK inhibition and the silencing of Wnt-11 showed similar responses in DU145 and PC-3 cells and decreased metastasis-related biomarkers, cell migration, and invasion. Overall, our results suggest that JNK signalling plays a significant role in the pathophysiology of PCa by mediating Wnt-11 induced signals. Our data highlights that both the JNK pathway and Wnt-11 could be a useful therapeutic target for the combinatory application of current PCa.

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Upregulated Wnt-11 and miR-21 Expression Trigger Epithelial Mesenchymal Transition in Aggressive Prostate Cancer Cells

Cited by 27 publications

References 41 publications

MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells

MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells

Altered expression of microRNA‑92b‑3p predicts survival outcomes of patients with prostate cancer and functions as an oncogene in tumor progression

Inhibition on JNK Mimics Silencing of Wnt-11 Mediated Cellular Response in Androgen-Independent Prostate Cancer Cells

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