MiRNA-200a induce cell apoptosis in renal cell carcinoma by directly targeting SIRT1

Fu, Hao; Song, Wenke; Chen, Xuancai; Guo, Tao; Duan, Bin; Xin-xi, Wang; Tang, Yunhui; Huang, Liang; Liu, Yi-Zhang

doi:10.1007/s11010-017-3102-1

Cited by 22 publications

(16 citation statements)

References 26 publications

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“…In the past decades, the roles of cellular miRNA abnormalities in the pathogenesis of most human cancers have been intensely investigated. [25][26][27] Furthermore, the miR-200a-3p/ CBL pathway has not been explored in RCC. In the current study, we focused on understanding the pathological roles of miR-200a-3p in RCC.…”

Section: Discussionmentioning

confidence: 99%

“…[26][27][28] To further uncover the underlying mechanisms of the suppression of RCC cell growth and migration mediated by miR-200a-3p, we searched for miRNA targets and identified CBL as a novel target of miR-200a-3p. [26][27][28] To further uncover the underlying mechanisms of the suppression of RCC cell growth and migration mediated by miR-200a-3p, we searched for miRNA targets and identified CBL as a novel target of miR-200a-3p.…”

Section: Discussionmentioning

confidence: 99%

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Decreased miR‐200a‐3p is a key regulator of renal carcinoma growth and migration by directly targeting CBL

Ding

Sun

Zhong

et al. 2018

J of Cellular Biochemistry

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Although emerging evidence has revealed that microRNAs (miRNAs) dysregulation contribute to carcinogenesis, the mechanism underlying their roles in renal cell carcinoma (RCC) is unclear. The purpose of the current study was to analyze the association of miR-200a-3p expression with RCC and to understand potential novel target genes, functions and mechanisms of miR-200a-3p in RCC. MiR-200a-3p expression levels were first measured by quantitative real-time polymerase chain reaction and in situ hybridization in pairs of RCC tissue samples. Next, the potential miR-200a-3p target gene was analyzed using a combination of computer-aided algorithms, luciferase reporter assays and Western blot analysis. Finally, the biological roles of miR-200a-3p in RCC tumorigenesis were investigated both in vitro by 5-ethynyl-20-deoxyuridine, apoptosis assay and transwell assay, as well as in vivo using a xenograft mouse model. Our results demonstrated that miR-200a-3p was remarkably downregulated in RCC tissues compared with normal adjacent tissue, and CBL is a direct target of miR-200a-3p. An inverse correlation between miR-200a-3p and CBL was observed in RCC tissue samples. Mechanistic investigations revealed that ectopic expression of miR-200a-3p in RCC cell lines suppressed cell proliferation and migration and enforced cell apoptosis by directly inhibiting CBL in vitro and in vivo, whereas silencing miR-200a-3p resulted in the opposite effects. Additionally, overexpressing CBL abolished the effects induced by miR-200a-3p overexpression. Taken together, our results show that the miR-200a-3p/CBL regulation axis is a novel mechanism underlying RCC pathogenesis and may serve as a candidate biomarker and therapeutic target in RCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Decreased miR‐200a‐3p is a key regulator of renal carcinoma growth and migration by directly targeting CBL

Ding

Sun

Zhong

et al. 2018

J of Cellular Biochemistry

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“…transcription factors and transcriptional coregulators as well as miRNAs [9,15,18,24,39]. Our previous studies have demonstrated that the GMC apoptosis evoked by sublytic C5b-9 in rat Thy-1N is associated with the upregulation of some specific transcription factors (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…IRF-1 acetylation by p300) [15,18,20]. Recently, several experiments have revealed that miR-200a and miR-1469 are involved in regulating cell apoptosis [24,40]. Given that miRNAs can affect target gene expression by binding to the complementary sites of mRNAs 3` UTR causing mRNA degradation or translation inhibition [21,23], and many researchers have found that miRNAs such as miR-148b, miR-29c and miR-29b are important regulators of viral infection, cancer or diabetes including MsPGN [24-28, 39, 41], the effects of miRNAs on the GMC apoptosis mediated by sublytic C5b-9 in Thy-1N rats and the underlying mechanism needs to be explored.…”

Section: Discussionmentioning

confidence: 99%

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Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis Through miR-3546/SOX4/Survivin Axis in Rat Thy-1 Nephritis

Yao

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: The activation of complement system and the formation of C5b-9 complex have been confirmed in the glomeruli of patients with mesangioproliferative glomerulonephritis (MsPGN). However, the role and mechanism of C5b-9-induced injury in glomerular mesangial cell (GMC) are poorly understood. Rat Thy-1N is an animal model for studying MsPGN. It has been revealed that the attack of C5b-9 to the GMC in rat Thy-1N is sublytic, and sublytic C5b-9 can cause GMC apoptosis, but the underlying mechanism is not fully elucidated. To explore the role and regulatory mechanism of C5b-9 in MsPGN lesion, we used rat Thy-1N model and first detected the change of microRNA (miRNA) profiles both in Thy-1N rat renal tissues (in vivo) and in the cultured GMCs with sublytic C5b-9 stimulation (in vitro). Then we determined the effect of miR-3546, which increased both in vivo and in vitro, on GMC apoptosis upon sublytic C5b-9 as well as the involved mechanism. Methods: Rat Thy-1N model was established and GMCs were treated with sublytic C5b-9. The rat renal cortex and the stimulated GMCs were obtained for miRNA microarray detection. Subsequently, the increased miRNAs were verified by real-time PCR. Meanwhile, to ascertain the ability of some miRNAs to upregulate cleaved caspase 3 and induce GMC apoptosis, the corresponding miRNA mimics were transfected into GMCs, followed by western blotting (WB) and flow cytometry mesurement. Thereafter, the miR-3546-targeted gene (SOX4) was predicted using bioinformatics approaches, and SOX4 expression in Thy-1N tissues and in the GMCs upon sublytic C5b-9 stimulation or miR-3546 mimic/inhibitor transfection were detected using real-time PCR and WB. To prove that miR-3546 can affect SOX4 gene transcription and SOX4 can regulate survivin expression, dual luciferase reporter assay, real-time PCR, WB and chromatin immunoprecipitation (ChIP) assays were performed. Furthermore, the role of miR-3546/SOX4/survivin axis in the GMC apoptosis induced by sublytic C5b-9 was examined using WB and flow cytometry. Results: Compared with normal renal tissues and untreated GMCs, there were 43 and 62 upregulated miRNAs (> 2-fold) in Thy-1N tissues and sublytic C5b-9-stimulated GMCs respectively. A total of 17 miRNAs were increased both in vivo and in vitro, 11 of which were validated by real-time PCR. Among them, miR-3546 could markedly promote GMC apoptosis and inhibit SOX4 or survivin expression in response to sublytic C5b-9, and either SOX4 or survivin overexpression markedly rescued the GMC apoptosis mediated by miR-3546 mimic. Additionally, SOX4 overexpression could reverse the survivin suppression by miR-3546 mimic, and SOX4 could bind to survivin promoter (-1,278 to -853 nt) and activate survivin gene transcription. Conclusion: MiR-3546/ SOX4/survivin axis has a promoting role in the GMC apoptosis triggered by sublytic C5b-9, and our findings may provide a new insight into the pathogenesis of rat Thy-1N and human MsPGN.

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Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer

Oto

Plana²,

Sánchez-González³

et al. 2020

Curr Urol Rep

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MiRNA-200a induce cell apoptosis in renal cell carcinoma by directly targeting SIRT1

Cited by 22 publications

References 26 publications

Decreased miR‐200a‐3p is a key regulator of renal carcinoma growth and migration by directly targeting CBL

Decreased miR‐200a‐3p is a key regulator of renal carcinoma growth and migration by directly targeting CBL

Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis Through miR-3546/SOX4/Survivin Axis in Rat Thy-1 Nephritis

Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer

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