The RNA binding protein RBMS3 inhibits the metastasis of breast cancer by regulating Twist1 expression

Abstract

Background Metastasis remains the biggest obstacle for breast cancer treatment. Therefore, identification of specific biomarker of metastasis is very necessary. The RNA binding protein 3 (RBMS3) acts as a tumor suppressor in various cancers. Whereas, its role and underlying molecular mechanism in breast cancer is far from elucidated. Methods Quantitative real-time PCR and western blots were carried out to determine the expression of RBMS3 in breast cancer cells and tissues. Transwell and in vivo metastasis assay were conducted to investigate the effects of RBMS3 on migration, invasion and metastasis of breast cancer cells. Transcriptome sequencing was applied to screen out the differential gene expression affected by RBMS3. RNA immunoprecipitation assay combined with luciferase reporter assay were performed to explore the direct correlation between RBMS3 and Twist1 mRNA. Results RBMS3 was downregulated in breast cancer and ectopic expression of RBMS3 contributed to inhibition of cell migration, invasion in vitro and lung metastasis in vivo. Furthermore, RBMS3 negatively regulated Twsit1 expression via directly binding to 3′-UTR of Twist1 mRNA, and thereby decreased Twist1-induced expression of matrix metalloproteinase 2 (MMP2). Additionally, Twist1-induced cell migration, invasion and lung metastasis could be reversed by the upregulation of RBMS3. Conclusions In summary, our study revealed a novel mechanism of the RBMS3/Twsit1/MMP2 axis in the regulation of invasion and metastasis of breast cancer, which may become a potential molecular marker for breast cancer treatment.

Dysregulated lncRNA-miRNA-mRNA Network Reveals Patient Survival-Associated Modules and RNA Binding Proteins in Invasive Breast Carcinoma

“…However, these two miRNAs were down-regulated in breast cancer, which means that the inhibition was lost, contributing to the development of breast cancer. Consistent with the tumorsuppressive role of these two miRNAs, TGFBR3 was reported to suppress breast cancer progression through TGF-beta signaling (Lee et al, 2010), and RBMS3 and PTPN14 were also shown to play roles in inhibiting metastasis (Belle et al, 2015;Zhu et al, 2019a). These data imply that the function of module 1 may be to inhibit cancer progress and metastasis and that these functional miRNAs may affect breast cancer through TGFBR3, RBMS3, and PTPN14.…”

“…TGFBR3 inhibits breast cancer progression through TGF-beta signaling (Lee et al, 2010). In addition, other molecules in module 1 such as ADAMTS5 (Fontanil et al, 2017), ARHGAP20 (Asaduzzaman et al, 2017), C2orf88 (Lo et al, 2015), EZH1 (Liu et al, 2012), FAM13A (Goto-Yamaguchi et al, 2018), FGF1 (Slattery et al, 2013), GNAL (Yi et al, 2009), GRAMD3 (Boiles et al, 2015), PELI2 (Zang et al, 2017), PLSCR4 (Sahay et al, 2015), PTPN14 (Belle et al, 2015), RBMS3 (Zhu et al, 2019a), SH3BGRL2 (Alexe et al, 2007;Wen et al, 2018), let-7c (Fu et al, 2017), mir-100 (Jiang et al, 2016b), mir-10b (Wang et al, 2016b), mir-125b (Wang et al, 2019a), mir-139 (Dai et al, 2017), and mir-21 (Yan et al, 2008;Yanwirasti and Arisanty, 2017;Zhu et al, 2019b) have been reported to play important roles in breast cancer. Module 2 had nine nodes, including two miRNAs, five lncRNAs, and two protein-coding genes.…”

Oncogenic action of the exosome cofactor RBM7 by stabilization of CDK1 mRNA in breast cancer

“…It was previously found that two other RBMs, RBM38 and RBMS2 acted as tumor suppressor in breast cancers 19 , 22 . Yang et al also found RBMS3 could inhibit breast cancer proliferation and metastasis 31 , 32 . In the present study, RBM7 firstly served as a breast cancer oncogene.…”

Different roles of matrix metalloproteinase 2 in osteolysis of skeletal dysplasia and bone metastasis (Review)

“…Overexpression of MMP2 is usually detected in cancer, and its protein expression levels positively correlate with factors that indicate a poor prognosis, such as poor differentiation, metastasis to secondary organs and chemotherapy resistance ( 14 , 15 ). For instance, in breast cancer, increased expression of MMP2 protein is associated with Twist1-induced invasion and metastasis, whereas decreased MMP2 protein expression levels are involved in RNA binding motif single-stranded interacting protein 3 (RBMS3)-mediated tumor suppression via the RBMS3/Twist1/MMP2 axis ( 16 ). Similarly, the protein expression level of MMP2 in pulmonary tumors is notably elevated, which affects the metastatic properties of tumors through a variety of signaling pathways, such as the sphingolipid and ephrin receptor-signaling pathway ( 17 ).…”