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.

MECP2 promotes migration and invasion of gastric cancer cells via modulating the Notch1/c-Myc/mTOR signaling pathways by suppressing FBXW7 transcription

“…This nding is consistent with that of some previous studies which show that MECP2 functions as a transcriptional repressor by binding to the methylated CpG sites of gene promoter regions and recruiting corepressors (e.g. histone deacetylases and Sin3A), to restrain the expression of some genes (e.g., MYOD1, FOXF1, BDNF, Cdkl5, RPL11 and RPL5) [17,20,21]. FBXW7, a member of the F-box family of proteins, has been characterized as a tumor suppressor gene that plays an important function in cancer cell survival, proliferation, cycle, apoptosis, differentiation, metabolism, tumor metastasis and drug resistance [40,41].…”

“…Recent research has found that MECP2 regulates cancer cell migration and invasion in glioma and breast cancer [32,33]. Our previous studies have proved that MECP2 promotes cell proliferation and cell cycle G1-S transition, and restrains cell apoptosis in liver cancer, gastric cancer and breast cancer [19][20][21][22]. By expanding sample, the present study aims to further identify the effect and the molecular mechanism of MECP2 on GC cell migration and invasion.…”

“…In recent years, emerging evidence indicates the role of MECP2 as a crucial oncogene in several cancer types [18]. Our previous studies have found that MECP2 is upregulated in liver cancer and facilitates cell growth [19], it enhances breast cancer proliferation via facilitating ubiquitination-mediated P53 degradation by regulating RPL5/RPL11 expressions [20], and it promotes GC cell proliferation and suppresses cell apoptosis via restraining FOXF1/MYOD1 transcription and enhancing GIT1 transcription by binding to the methylated CpG sites of the promoter regions of FOXF1/MYOD1 [21,22]. Cancer cell migration and invasion are related to the metastatic potential of the cells, which may be independent of cell proliferation rates.…”

A systems based framework to computationally predict putative transcription factors and signaling pathways regulating glycan biosynthesis

“…MECP2 regulates gene expression by binding to methylated promoters, and then by recruiting chromatin remodeling proteins to condense DNA and repress gene expression 31,32 . In breast cancer, it is thought that MEPC2 inhibits the p53 pathway via the epigenetic upregulation of RPL5 and RPL11, thus causing cancer proliferation 33 .…”

Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1

“…Breast cancer is one of the most common tumors and the second leading cause of cancer-related deaths in women. 1 Although the development of antitumor drugs and diagnostic methods have greatly improved the overall survival rates of patients with breast cancer, the metastatic breast cancer hampered the effectiveness of antitumor drugs. 2 Considering that plenty of factors, including chemokines, cytokines or growth factors, have been shown to be responsible for the metastasis of breast cancer, 3 the molecular mechanisms involved in tumor growth, migration and invasion have not been fully elucidated.…”