The RASSF6 Tumor Suppressor Protein Regulates Apoptosis and the Cell Cycle via MDM2 Protein and p53 Protein

Iwasa, Hiroaki; Kudo, Takumi; Maimaiti, Sainawaer; Ikeda, Mitsunobu; Maruyama, Junichi; Nakagawa, Kentaro; Hata, Yoshinobu

doi:10.1074/jbc.m113.507384

Cited by 48 publications

(79 citation statements)

References 28 publications

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“…[47][48][49] RASSF6 played as a tumour suppressor gene and suppressed tumour cell growth, invasion and migration and promoted the cell cycle and apoptosis. 48,50 In this study, we demonstrated that RASSF6 expression was downregulated in osteosarcoma tissues and cell lines and downregulated expression of RASSF6 was correlated with advanced TNM stage. Moreover, the expression of RASSF6 was positively correlated with the expression of CASC2 in osteosarcoma tissues.…”

Section: Discussionmentioning

confidence: 85%

Downregulation of lncRNA CASC2 facilitates osteosarcoma growth and invasion through miR‐181a

Hao

et al. 2017

Cell Proliferation

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Objectives: Long non-coding RNA cancer susceptibility candidate 2 (CASC2) is a novel lncRNA and has been indicated as playing tumour suppressor gene in several tumours.However, the role of CASC2 in osteosarcoma is still uncovered. Materials and methods:The CASC2 and miR-181a expressions were measured via qRT-PCR. CCK-8 assay and colony formation assay were performed to determine the cell growth, and transwell assay was performed to assess the cell invasion. Results:We showed that CASC2 expression was downregulated in osteosarcoma samples and cell lines. Moreover, we showed that downregulated expression of CASC2 was correlated with advanced TNM stage. Furthermore, overexpression of CASC2 inhibited osteosarcoma cell proliferation, colony formation, and invasion. In addition, we indicated that ectopic expression of CASC2 suppressed miR-181a expression and enhanced the expression of Ras association domain family member 6 (RASSF6), PTEN and ATM in osteosarcoma cell, which were the direct target gene of miR-181a. Moreover, we indicated that RASSF6 expression was downregulated in osteosarcoma samples and cell lines and downregulated expression of RASSF6 was correlated with advanced TNM stage. We found that the expression of RASSF6 was positively correlated with the expression of CASC2 in osteosarcoma tissues. Ectopic expression of CASC2 suppressed the osteosarcoma cell proliferation, colony formation and invasion through regulating RASSF6 expression. Conclusions:Our data illuminated that CASC2 acted as a tumour suppressor in osteosarcoma progression.

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Section: Discussionmentioning

confidence: 85%

Downregulation of lncRNA CASC2 facilitates osteosarcoma growth and invasion through miR‐181a

Hao

et al. 2017

Cell Proliferation

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“…RASSF6 association with MST2 inhibits canonical Hippo pathway activation [93]. Interestingly, it was demonstrated that RASSF6 binds to MDM2 and facilitates its self ubiquitination and degradation, stabilizing p53 (like RASSF1A and RASSF3), thereby regulating apoptosis and cell cycle [94]. It also has been demonstrated that, similar to RASSF1A and RASSF2, RASSF6 can inhibit NFjB activity and possibly inflammation by unknown mechanisms [87].…”

Section: Rassf6mentioning

confidence: 99%

RASSF tumor suppressor gene family: Biological functions and regulation

et al. 2014

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a b s t r a c tGenetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The RASSF (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, RASSF proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate NFjB activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the RASSF family members and their regulation.

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“…37,38,46 In the latest published finding, Iwasa showed that RASSF6 regulates apoptosis and the cell cycle via stabilization of p53. 47 Interestingly, in our study, we did not observe any changes in p53 expression related to RASSF6 in ccRCC, and we therefore suspect that RASSF6-induced cell cycle arrest and apoptosis in ccRCC is not dependent on p53 levels.…”

Section: Discussionmentioning

confidence: 59%

RASSF6promotes p21^Cip1/Waf1-dependent cell cycle arrest and apoptosis through activation of the JNK/SAPK pathway in clear cell renal cell carcinoma

Liang

Zheng

et al. 2014

Cell Cycle

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The RASSF6 Tumor Suppressor Protein Regulates Apoptosis and the Cell Cycle via MDM2 Protein and p53 Protein

Abstract: Background: RASSF6 is a proapoptotic protein related to the Hippo pathway. Results: RASSF6 interacts with MDM2 and stabilizes p53. Conclusion: RASSF6 induces apoptosis and cell cycle arrest via p53. Significance: Our work supports the importance of the C-terminal RASSF-MDM2-p53 axis.

Cited by 48 publications

References 28 publications

Downregulation of lncRNA CASC2 facilitates osteosarcoma growth and invasion through miR‐181a

Downregulation of lncRNA CASC2 facilitates osteosarcoma growth and invasion through miR‐181a

RASSF tumor suppressor gene family: Biological functions and regulation

RASSF6promotes p21^Cip1/Waf1-dependent cell cycle arrest and apoptosis through activation of the JNK/SAPK pathway in clear cell renal cell carcinoma

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The RASSF6 Tumor Suppressor Protein Regulates Apoptosis and the Cell Cycle via MDM2 Protein and p53 Protein

Abstract: Background: RASSF6 is a proapoptotic protein related to the Hippo pathway. Results: RASSF6 interacts with MDM2 and stabilizes p53. Conclusion: RASSF6 induces apoptosis and cell cycle arrest via p53. Significance: Our work supports the importance of the C-terminal RASSF-MDM2-p53 axis.

Cited by 48 publications

References 28 publications

Downregulation of lncRNA CASC2 facilitates osteosarcoma growth and invasion through miR‐181a

Downregulation of lncRNA CASC2 facilitates osteosarcoma growth and invasion through miR‐181a

RASSF tumor suppressor gene family: Biological functions and regulation

RASSF6promotes p21Cip1/Waf1-dependent cell cycle arrest and apoptosis through activation of the JNK/SAPK pathway in clear cell renal cell carcinoma

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RASSF6promotes p21^Cip1/Waf1-dependent cell cycle arrest and apoptosis through activation of the JNK/SAPK pathway in clear cell renal cell carcinoma