ArticleOncoTargets and therapy2019
RASSF6 Is Downregulated In Human Bladder Cancers And Regulates Doxorubicin Sensitivity And Mitochondrial Membrane Potential Via The Hippo Signaling Pathway.
Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 16 citations in OpenAlex.
- Transcriptomic and Metabolomic Profiling Reveals the Antiproliferative Mechanism of Goose Serum and Plasma in SW1990 Cells.Biology · 2026Article
- Hippo Signaling Dysregulation in Breast Cancer: Subtype-Independent Gene and miRNA Signatures.Biomedicines · 2025Article
- YAP activation in Müller cells protects against NMDA-induced retinal ganglion cell injury by regulating Bcl-xL expression.Frontiers in pharmacology · 2024Article
- Cell death regulation in myocardial toxicity induced by antineoplastic drugs.Frontiers in cell and developmental biology · 2023Review
- DNA Damage Triggers the Nuclear Accumulation of RASSF6 Tumor Suppressor Protein via CDK9 and BAF53 To Regulate p53 Target Gene Transcription.Molecular and cellular biology · 2022Article
- Context-dependent roles of YAP/TAZ in stem cell fates and cancer.Cellular and molecular life sciences : CMLS · 2021Review
- Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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Abstract
backgroundThe present study aimed to investigate the clinicopathological significance and biological roles of RASSF6 in human bladder cancers. MATERIALS AND
methodsImmunohistochemistry and Western blots were used to examine the protein expression of RASSF6 in bladder cancer tissues. Biological roles of RASSF6 were examined using MTT, colony formation assay, Matrigel invasion assay, cell cycle analysis, AnnexinV/PI staining and JC-1 staining. Western blot analysis was used to examine the potential mechanism.
resultsWe found that RASSF6 was downregulated in 73 of 138 bladder cancer specimens, which correlated with advanced stages. RASSF6 overexpression decreased the cell growth rate and inhibited invasion ability in T24 cell line. Downregulation of RASSF6 using siRNA increased the cell proliferation rate and promoted invasion in 5637 cell line. Cell cycle studies showed that RASSF6 overexpression suppressed the process of cell cycle progression. RASSF6 overexpression also increased the cellular response to doxorubicin (DOX) treatment. AnnexinV/PI staining showed that RASSF6 overexpression promoted DOX-induced apoptosis with increased cytochrome c and cleavage of caspase-3 and caspase-9. We also showed that RASSF6 overexpression downregulated the mitochondrial membrane potential, while RASSF6 depletion showed the opposite effect. Western blot analysis demonstrated that RASSF6 overexpression repressed p-Rb and Bcl-xL while upregulating p21 expression. In addition, we found that RASSF6 overexpression affected the Hippo signaling pathway by downregulating YAP. Depletion of YAP downregulated Bcl-xL expression and abolished the effect of RASSF6 on Bcl-xL. Depletion of YAP also upregulated the level of apoptosis and downregulated mitochondrial membrane potential. YAP siRNA abolished the effects of RASSF6 on DOX-induced apoptosis and loss of mitochondrial membrane potential.
conclusionTaken together, our results showed that RASSF6 was downregulated in bladder cancers. RASSF6 inhibited cell proliferation and invasion, as well as the progression of cancer, by regulating DOX sensitivity and mitochondrial membrane potential, possibly via the Hippo signaling pathway.
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