MiR-429 is linked to metastasis and poor prognosis in renal cell carcinoma by affecting epithelial-mesenchymal transition

Macháčková, Táňa; Mlčochová, Hana; Staník, Michal; Doležel, Jan; Fedorko, Michal; Pacík, Dalibor; Poprach, Alexandr; Svoboda, Marek; Slabý, Ondřej

doi:10.1007/s13277-016-5310-9

Cited by 40 publications

(26 citation statements)

References 29 publications

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“…MicroRNA expression patterns have been reported to be more accurate in establishing the right diagnosis than the mRNA criteria, in poorly differentiated metastatic cancer cases with cancer of unknown primary origin (45). In ccRCC, miRNA-429 was found to be a potential diagnostic and prognostic biomarker and a potential regulator of EMT(46). miR-429 was significantly associated with cancer metastasis, shorter disease-free and overall survival(46).…”

Section: Discussionmentioning

confidence: 99%

“…In ccRCC, miRNA-429 was found to be a potential diagnostic and prognostic biomarker and a potential regulator of EMT(46). miR-429 was significantly associated with cancer metastasis, shorter disease-free and overall survival(46). Our results reveal that miR-720 expression can robustly (p<0.0001) discriminate malignant from non-malignant tissues and hence can be used as a diagnostic marker for RCC.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-720 Regulates E-cadherin–αE-catenin Complex and Promotes Renal Cell Carcinoma

Bhat

Colden

Dar

et al. 2017

Molecular Cancer Therapeutics

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MicroRNAs are implicated in regulating cancer progression and metastasis. Here we show that miR-720 is positively associated with renal cell carcinoma (RCC). Elevated levels of miR-720 were observed in a panel of RCC cell lines and clinical tissues compared to non-malignant cell line and normal samples. Loss of miR-720 function inhibited proliferation, migration and invasion and induced apoptosis in RCC cell lines in vitro and repressed tumor growth in xenograft mouse model. Conversely, gain of miR-720 function in non-malignant HK-2 cells induced pro-cancerous characteristics. Silencing of miR-720 caused a marked induction in the levels of endogenous αE-catenin and E-cadherin protein levels in anti720 transfected cells compared to control. Whereas, miR-720 overexpression in RCC cell lines reduced activity of a luciferase reporter gene fused to the wild-type αE-catenin or E-cadherin 3′ UTR compared to non-specific 3′ UTR control indicating that αE-catenin-E-cadherin complex is a direct and functional target of miR-720 in RCC. We also observed attenuation of β-Catenin, CD44 and Akt expression in RCC cells transfected with miR-720 inhibitor compared to control. Further, miR-720 exhibited clinical significance in RCC. Expression of miR-720 significantly distinguished malignant from normal samples. Elevated miR-720 levels positively correlated with higher Fuhrman grade, pathological stage and poor overall survival of RCC patients. These findings uncover a new regulatory network in RCC involving metastasis-promoting miR-720 that directly targets expression of key metastasis-suppressing proteins E-cadherin and αE-catenin complex. These results suggest that therapeutic regulation of miR-720 may provide an opportunity to regulate EMT and metastasis in RCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-720 Regulates E-cadherin–αE-catenin Complex and Promotes Renal Cell Carcinoma

Bhat

Colden

Dar

et al. 2017

Molecular Cancer Therapeutics

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“…However, the role of miR-429 is controversial. Machackova et al reported that miR-429 acts as a tumor suppressor by inhibiting the loss of E-cadherin in RCC cells (23). miR-429 can also inhibit the migration, invasion, and proliferation of RCC cells by targeting Sp1 directly (15).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑429 inhibits cancer cell proliferation and migration by targeting AKT1 in renal cell carcinoma

Jiang

Chen

et al. 2019

mol clin onc

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MicroRNAs (miRNAs or miR) serve as oncogenes and tumor suppressors. In a previous study, it was revealed that has-miRNA-429 (miR-429) is a tumor suppressor in 786-O renal cell carcinoma (RCC) cells. However, its mechanism in RCC remains to be determined. The present study aimed to explain the functional role and mechanism of miR-429 in RCC pathogenesis. Luciferase reporter assays demonstrated that miR-429 overexpression reduced the transcriptional activity of AKT serine/threonine kinase 1 (AKT1). Reverse transcripton-quantitative (RT-q) PCR and western blot analysis indicated that the mRNA and protein expression of AKT1 was downregulated in 786-O RCC cell lines when miR-429 was overexpressed, indicating that miR-429 may directly target AKT1 in RCC. Therefore, miR-429 overexpression enhanced the inhibition of tumor size and weight in nude mice in vivo. The current study indicated that the novel miR-429-regulated pathway may provide insights into RCC oncogenesis and metastasis.

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“…Zinc finger E‐box binding homeobox 1 and Crk‐like have also been identified as direct target responsible for the inhibitory effect of miR‐429 on cell migration and invasion in breast cancer cells . MiR‐429 is aberrantly downregulated in renal cell carcinoma and associated with longer patients' survival . Furthermore, the antitumour effect of miR‐429 on gastric carcinoma cells, cervical cancer cells and bladder cancer cells have also been documented.…”

Section: Discussionmentioning

confidence: 99%

“…41 MiR-429 is aberrantly downregulated in renal cell carcinoma and associated with longer patients' survival. 42 Furthermore, the antitumour effect of miR-429 on gastric carcinoma cells, 43 cervical cancer cells 44 and bladder cancer FIGURE 5 SOX2 mediates the antitumour effect of miR-429 in GBM cells. A, SOX2 expression is successfully restored in GBM cells.…”

Section: Discussionmentioning

confidence: 99%

MiR‐429 suppresses glioblastoma multiforme by targeting SOX2

Dong

Hao

Cui

et al. 2017

Cell Biochemistry & Function

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Accumulating evidence has shown that miR-429 plays an important role in the development and progression of tumour. However, the role of miR-429 in glioblastoma multiforme (GBM) remains largely unknown. The present study is designed to investigate the function of miR-429 in GBM and to explore the molecular mechanism underlying its function. The expression level of miR-429 was detected in GBM tissues and cell lines by quantitative real-time polymerase chain reaction. The effect of overexpression of miR-429 on in vitro cell proliferation, apoptosis and invasion was examined. Western blot analysis was used to detect the influence of miR-429 on the expression of target gene, and Pearson analysis was used to calculate the correlation between the expression of targets gene and the miR-429 in GBM tissues. Our study shows that miR-429 is downregulated in GBM tissues compared with noncancerous tissues (P < .01). In addition, the expression of miR-429 in GBM cell lines is also significantly lower (P < .01). Enforced expression of miR-429 inhibits GBM cells proliferation, induces apoptosis and suppresses invasion and leads to the downregulation of the SOX2 protein. Moreover, the expression level of miR-429 in GBM tissues shows inverse relationship with the expression level of SOX2 protein. Our findings suggest that miR-429 represents a potential tumour-suppressive miRNA and plays an important role in GBM progression by directly targeting SOX2.

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MiR-429 is linked to metastasis and poor prognosis in renal cell carcinoma by affecting epithelial-mesenchymal transition

Cited by 40 publications

References 29 publications

MicroRNA-720 Regulates E-cadherin–αE-catenin Complex and Promotes Renal Cell Carcinoma

MicroRNA-720 Regulates E-cadherin–αE-catenin Complex and Promotes Renal Cell Carcinoma

MicroRNA‑429 inhibits cancer cell proliferation and migration by targeting AKT1 in renal cell carcinoma

MiR‐429 suppresses glioblastoma multiforme by targeting SOX2

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