Dataset Information

MeCP2 facilitates breast cancer growth via promoting ubiquitination-mediated P53 degradation by inhibiting RPL5/RPL11 transcription.

ABSTRACT: Methyl-CpG-binding protein 2 (MeCP2) facilitates the carcinogenesis and progression of several types of cancer. However, its role in breast cancer and the relevant molecular mechanism remain largely unclear. In this study, analysis of the Cancer Genome Atlas (TCGA) data that MeCP2 expression was significantly upregulated in breast cancer tissues, and high MeCP2 expression was correlated with poor overall survival. Knockdown of MeCP2 inhibited breast cancer cell proliferation and G1-S cell cycle transition and migration as well as induced cell apoptosis in vitro. Moreover, MeCP2 knockdown suppressed cancer cell growth in vivo. Investigation of the molecular mechanism showed that MeCP2 repressed RPL11 and RPL5 transcription by binding to their promoter regions. TCGA data revealed significantly lower RPL11 and RPL5 expression in breast cancer tissues; additionally, overexpression of RPL11/RPL5 significantly suppressed breast cancer cell proliferation and G1-S cell cycle transition and induced apoptosis in vitro. Furthermore, RPL11 and RPL5 suppressed ubiquitination-mediated P53 degradation through direct binding to MDM2. This study demonstrates that MeCP2 promotes breast cancer cell proliferation and inhibits apoptosis through suppressing RPL11 and RPL5 transcription by binding to their promoter regions.

SUBMITTER: Tong D

PROVIDER: S-EPMC7264296 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MeCP2 facilitates breast cancer growth via promoting ubiquitination-mediated P53 degradation by inhibiting RPL5/RPL11 transcription.

Tong DongDong D Zhang Jing J Wang XiaoFei X Li Qian Q Liu Li Ying LY Yang Juan J Guo Bo B Ni Lei L Zhao LingYu L Huang Chen C

Oncogenesis 20200601 5

Methyl-CpG-binding protein 2 (MeCP2) facilitates the carcinogenesis and progression of several types of cancer. However, its role in breast cancer and the relevant molecular mechanism remain largely unclear. In this study, analysis of the Cancer Genome Atlas (TCGA) data that MeCP2 expression was significantly upregulated in breast cancer tissues, and high MeCP2 expression was correlated with poor overall survival. Knockdown of MeCP2 inhibited breast cancer cell proliferation and G1-S cell cycle ...[more]

PMID: 32483207

Similar Datasets

Project description:BackgroundPax3 is a developmental transcription factor that is required for neural tube and neural crest development. We previously showed that inactivating the p53 tumor suppressor protein prevents neural tube and cardiac neural crest defects in Pax3-mutant mouse embryos. This demonstrates that Pax3 regulates these processes by blocking p53 function. Here we investigated the mechanism by which Pax3 blocks p53 function.Methodology/principal findingsWe employed murine embryonic stem cell (ESC)-derived neuronal precursors as a cell culture model of embryonic neuroepithelium or neural crest. Pax3 reduced p53 protein stability, but had no effect on p53 mRNA levels or the rate of p53 synthesis. Full length Pax3 as well as fragments that contained either the DNA-binding paired box or the homeodomain, expressed as GST or FLAG fusion proteins, physically associated with p53 and Mdm2 both in vitro and in vivo. In contrast, Splotch Pax3, which causes neural tube and neural crest defects in homozygous embryos, bound weakly, or not at all, to p53 or Mdm2. The paired domain and homeodomain each stimulated Mdm2-mediated ubiquitination of p53 and p53 degradation in the absence of the Pax3 transcription regulatory domains, whereas Splotch Pax3 did not stimulate p53 ubiquitination or degradation.Conclusions/significancePax3 inactivates p53 function by stimulating its ubiquitination and degradation. This process utilizes the Pax3 paired domain and homeodomain but is independent of DNA-binding and transcription regulation. Because inactivating p53 is the only required Pax3 function during neural tube closure and cardiac neural crest development, and inactivating p53 does not require Pax3-dependent transcription regulation, this indicates that Pax3 is not required to function as a transcription factor during neural tube closure and cardiac neural crest development. These findings further suggest novel explanations for PAX3 functions in human diseases, such as in neural crest-derived cancers and Waardenburg syndrome types 1 and 3.

Dataset Information

MeCP2 facilitates breast cancer growth via promoting ubiquitination-mediated P53 degradation by inhibiting RPL5/RPL11 transcription.

Publications

MeCP2 facilitates breast cancer growth via promoting ubiquitination-mediated P53 degradation by inhibiting RPL5/RPL11 transcription.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure