MicroRNA-30e-3p inhibits cell invasion and migration in clear cell renal cell carcinoma by targeting Snail1

Chang

Journal of Cardiovascular Pharmacology

et al. 2017

Background:MicroRNAs are a class of small RNA molecules that inhibit protein expression through either degradation of messenger RNA or interference with protein translation. Our previous work suggested an involvement of miR-30e in myocardial fibrosis; however, the exact role of miR-30e in the pathogenesis of cardiac fibrosis and the underlying mechanisms are not known.Methods:Male Sprague Dawley rats were treated with isoproterenol (ISO) to induce cardiac remodeling and fibrosis and treated with either miR-30e agomir (AG) or antagomir and respective controls. The expression of miR-30e was evaluated by reverse transcription and quantitative polymerase chain reaction. Myocardial fibrosis was assessed by Masson's trichrome staining, and the level of oxidative stress and the expression of Snai1 and transforming growth factor-beta (TGF-β) were detected using Western blots.Results:A significant downregulation of miR-30e was found in the hearts of ISO-treated rats with cardiac fibrosis compared with nontreated controls. In vivo administration of miR-30e AG increased the survival of ISO-treated rats compared with AG-negative control administration, which was associated with reduced oxidative stress. We further identified Snai1 as a novel miR-30e target. Snai1 expression was significantly increased in hearts from ISO-treated rats, which coincided with decreased miR-30e expression and increased TGF-β expression. An miR-30e putative target sequence was identified in the 3′-untranslated region (UTR) Snai1. In a reporter assay, miR-30e greatly suppressed the activity of wild-type 3′-UTR–fused luciferase reporter, but showed no significant effect with the mutated 3′-UTR–fused reporter.Conclusion:MiR-30e attenuated ISO-induced cardiac dysfunction and cardiac fibrosis in a rat cardiac remodeling model. Mechanistically, miR-30e suppressed Snai1/TGF-β pathway which was involved in ISO-induced cardiac remodeling.

Section: Discussionsupporting

confidence: 73%

MiR-30e Attenuates Isoproterenol-induced Cardiac Fibrosis Through Suppressing Snai1/TGF-β Signaling

Chang

Journal of Cardiovascular Pharmacology

et al. 2017

“…no. ab52894; 1:50; Abcam) monoclonal antibodies, as previously described (20). The expression level was analyzed from images obtained using a light microscope (magnification, x200) from five random fields of view.…”

Section: Protein-protein Interaction (Ppi) Network Construction and Amentioning

confidence: 99%

“…The expression level was analyzed from images obtained using a light microscope (magnification, x200) from five random fields of view. Immunoblot assays were performed as previously described (20). Primary antibodies included those targeted against phosphorylated (p)-EGFR (cat.…”

Section: Protein-protein Interaction (Ppi) Network Construction and Amentioning

confidence: 99%

Ginkgolic acid inhibits the growth of renal cell carcinoma cells via inactivation of the EGFR signaling pathway

Zhu

Na²,

Huang³

et al. 2020

Exp Ther Med

Self Cite

Renal cell carcinoma (RCC) is one of the most common urological malignancies occurring in adult human kidneys worldwide. Recent research on antitumor drugs has focused on plant extracts, a class of compounds that play critical roles in cancer treatment. The present study aimed to investigate the potential antitumor effect of ginkgolic acid (GA) in RCC. Transwell invasion assay, cell counting kit-8 assay and flow cytometry were used to measure cell migration, cell viability and apoptosis, respectively. A network pharmacology approach was applied to identify pathway information, combining molecular docking techniques to screen for key target information. In the present study, GA inhibited the viability and proliferation of RCC cells (786-O and A498), both in vitro and in vivo, via G 1 arrest. GA also reduced RCC cell invasion and migration. In addition, the epidermal growth factor receptor (EGFR) was identified as a critical target protein of GA, which significantly inactivated EGFR signaling in RCC (P<0.05). Collectively, the present study provided evidence that GA exerts its anticancer function by directly targeting the EGFR signaling pathway, revealing the potential of GA therapy for RCC.

“…27), the most prevalent histological subtype, accounting for 70% to 80% of all RCC cases (28). For example, miRNAs have been implicated in different cellular processes in ccRCC, including proliferation, migration, invasion, and apoptosis (29,30). Recently, Yoshino and colleagues (31) targeted the two versions of miR-210, miR-210-3p and miR210-5p, employing the CRISPR/Cas9 system in three renal cell carcinoma (RCC) cell lines (786-o, A498 and Caki2).…”

Section: Renal Cell Carcinomamentioning

confidence: 99%

Emerging Role of CRISPR/Cas9 Technology for MicroRNAs Editing in Cancer Research

Aquino‐Jarquín

2017

Cancer Research

MicroRNAs (miRNA) are small, noncoding RNA molecules with a master role in the regulation of important tasks in different critical processes of cancer pathogenesis. Because there are different miRNAs implicated in all the stages of cancer, for example, functioning as oncogenes, this makes these small molecules suitable targets for cancer diagnosis and therapy. RNA-mediated interference has been one major approach for sequence-specific regulation of gene expression in eukaryotic organisms. Recently, the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system, first identified in bacteria and archaea as an adaptive immune response to invading genetic material, has been explored as a sequence-specific molecular tool for editing genomic sequences for basic research in life sciences and for therapeutic purposes. There is growing evidence that small noncoding RNAs, including miRNAs, can be targeted by the CRISPR/Cas9 system despite their lacking an open reading frame to evaluate functional loss. Thus, CRISPR/Cas9 technology represents a novel gene-editing strategy with compelling robustness, specificity, and stability for the modification of miRNA expression. Here, I summarize key features of current knowledge of genomic editing by CRISPR/Cas9 technology as a feasible strategy for globally interrogating miRNA gene function and miRNA-based therapeutic intervention. Alternative emerging strategies for nonviral delivery of CRISPR/Cas9 core components into human cells in a clinical context are also analyzed critically. .