Identification and characterization of a metastatic suppressor BRMS1L as a target gene of p53

Abstract

The tumor suppressor p53 and its family members, p63 and p73, play a pivotal role in the cell fate determination in response to diverse upstream signals. As transcription factors, p53 family proteins regulate a number of genes that are involved in cell cycle arrest, apoptosis, senescence, and maintenance of genomic stability. Recent studies revealed that p53 family proteins are important for the regulation of cell invasion and migration. Microarray analysis showed that breast cancer metastasis suppressor 1‐like (BRMS1L) is upregulated by p53 family proteins, specifically p53, TAp63γ, and TAp73β. We identified two responsive elements of p53 family proteins in the first intron and upstream of BRMS1L. These response elements are well conserved among mammals. Functional analysis showed that ectopic expression of BRMS1L inhibited cancer cell invasion and migration; knockdown of BRMS1L by siRNA induced the opposite effect. Importantly, clinical databases revealed that reduced BRMS1L expression correlated with poor prognosis in patients with breast and brain cancer. Together, these results strongly indicate that BRMS1L is one of the mediators downstream of the p53 pathway, and that it inhibits cancer cell invasion and migration, which are essential steps in cancer metastasis. Collectively, our results indicate that BRMS1L is involved in cancer cell invasion and migration, and could be a therapeutic target for cancer.

RETRACTED ARTICLE: Long non-coding RNA SATB2-AS1 inhibits microRNA-155-3p to suppress breast cancer cell growth by promoting breast cancer metastasis suppressor 1-like

“…Prediction tools, including TargetScan and microRNA.org were used to identify potential target genes of miR-155-3p. Among candidate genes, BRMS1L was selected due to its antitumor effect in human cancers [ 16 , 20 , 21 ]. To further test whether BRMS1L was a direct target of miR-155-3p, BRMS1L-WT reporter containing predicted miR-155-3p binding sites and BRMS1L-MUT reporter with mutant miR-155-3p binding sites were generated (Fig.…”

miR-93-5p enhance lacrimal gland adenoid cystic carcinoma cell tumorigenesis by targeting BRMS1L

“…3 a). BRMS1L plays an important role in cancer cell metastasis regulation [ 30 , 31 ]. We then examined whether miR-93-5p targets BRMS1L.…”

“…epidermal growth factor receptor (EGFR), osteopontin (OPN), phosphatidylinositol-4-phosphate 5-kinase 1 alpha (PI4P5K1A) and urokinase-plasminogen activator (PLAU) [ 21 ]. BRMS1L plays an important role in cancer cell metastasis regulation [ 30 , 31 ] such as breast cancer [ 22 ], melanoma [ 23 ], non-small cell lung [ 24 ] and ovarian cancer [ 16 ]. BRMS1L can be activated in many different signaling pathways.…”

Application of curcumin and its derivatives in tumor multidrug resistance

“…More than 500 genes were reported to be regulated by NF‐κB (Abouzeid, Patel, Sarisozen, & Torchilin, 2014). Moreover, p53 family members (p63 and p73) activate the transcription of MDR1 through indirect interaction with APE sites (Koyama et al, 2017; Van Nostrand, Bowen, Vogel, Barna, & Attardi, 2017). And CUR can inhibit many MDR‐related signal pathways such as NF‐κB, PI3K/Akt, and so on (Revalde, Li, Hawkins, Rosengren, & Paxton, 2015; Shakeri, Ward, Panahi, & Sahebkar, 2018).…”

“…The antitumor effect of CUR in lung cancer cells was affected by mir‐21, mir‐192‐5, mir‐215, mir‐186 and mir‐874. The target of mir‐186 was closely related with caspase‐10, the promoter of death receptor signal (Koyama et al, 2017). Studies confirmed that the resistance of A549/DDP cells and NSCLC (nonsmall cell lung cancer) to DDP and ADM was reversed with the treatment of CUR through down‐regulating the expression of HIF‐1α, mir‐186 gene (Zhang et al, 2010) and activating Caspase‐3 (Song et al, 2006; Ye, Zhao, et al, 2012; Figure 2).…”