Metastasis suppressor 1 controls osteoblast differentiation and bone homeostasis through regulating Src-Wnt/β-catenin signaling

Metastasis suppressor 1 (MTSS1) plays an inhibitory role in tumorigenesis and metastasis of a variety of cancers. To date, the function of MTSS1 in the differentiation of marrow stromal progenitor cells is completely unknown. In the current study, we explored whether and how MTSS1 has a role in osteoblast differentiation and bone homeostasis. Our data showed that MTSS1 mRNA was upregulated during osteoblast differentiation and downregulated in the osteoblastic lineage cells of ovariectomized and aged mice. Functional studies revealed that MTSS1 promoted the osteogenic differentiation from marrow stromal progenitor cells. Mechanistic explorations uncovered that the inactivation of Src and afterwards activation of canonical Wnt signaling were involved in osteoblast differentiation induced by MTSS1. The enhanced osteogenic differentiation induced by MTSS1 overexpression was attenuated when Src was simultaneously overexpressed, and conversely, the inhibition of osteogenic differentiation by MTSS1 siRNA was rescued when the Src inhibitor was supplemented to the culture. Finally, the in vivo transfection of MTSS1 siRNA to the marrow of mice significantly reduced the trabecular bone mass, along with the reduction of trabecular osteoblasts, the accumulation of marrow adipocytes, and the increase of phospho-Src positive cells on the trabeculae. No change in the number of osteoclasts was observed. This study has for the first time unraveled that MTSS1 contributes to osteoblast differentiation and bone homeostasis through regulating Src-Wnt/β-catenin signaling. It also suggests the potential of MTSS1 as a new target for the treatment of osteoporosis.

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

This article has been retracted. Please see the Retraction Notice for more detail: 10.1186/s12935-021-01798-y

PSIII-11 Effect of Breast cancer metastasis-suppressor 1-like (BRMS1L) genotype on teat number traits in Jeju native pigs (JNP) and Landrace

The purpose of this study was to compare the changes of teat number traits of Jeju native pig (JNP) and Landrace varieties according to the breast cancer metastasis-suppressor 1-like (BRMS1L) genotype. The number of teat varies according to the single-base polymorphism with a G or A base 1,087 from the start codon ATG in the exon 1 region of the BRMS1L gene. The total teat number was examined at birth for 28 JNPs and 72 Landraces, and the BRMS1L genotype was analyzed by Pyrosequencing. As a result, the genotyping frequency of JNP was 1 A / A type, 9 A / G type, and 18 G / G type, whereas, on the contrary, Landrace had 70 A / A type, 2 A / C type, and C / C was identified as 0 heads. The total teat number was between the two varieties was 13.32 ± 0.95 and 14.51 ± 1.03, respectively (P < 0.001). According to genotypes in Jeju native pig breeds, the total number of nipples was 15 A / A, 14.0 ± 0.82 A / G, and 12.89 ± 0.74 G / G (P < 0.018). Conversely, Landrace was 14.54 ± 1.02 A / A and 13.5 ± 0.5 A / G. As a result of the above study, the frequency of varieties and genotypes was found to have a significant effect on the difference in nipple count. Based on the results of this study, if the improvement of Jeju native pigs is to be carried out, it is expected that the number of nipples will increase and the mammalian capacity will increase.

miR-28-5p targets MTSS1 to regulate cell proliferation and apoptosis in esophageal cancer

Esophageal cancer (EC) is one of the most common aggressive malignant diseases worldwide. miR-28-5p plays important regulatory roles in many cancers including human EC. However, the molecular mechanism and potential role of miR-28-5p in EC remain uncertain. In this study, qRT-PCR and western blot analysis revealed that miR-28-5p expression was up-regulated and metastasis suppressor-1 (MTSS1) was down-regulated in EC tissues relative to matched para-cancer tissues. Cell counting kit-8 (CCK-8) assay demonstrated that miR-28-5p mimics increased cell viability, and miR-28-5p inhibitor decreased it. Flow cytometry (FCM) assay indicated that miR-28-5p mimics promoted cell cycle entry, while miR-28-5p inhibitor reduced it and induced cell apoptosis. Moreover, miR-28-5p mimics up-regulated the expressions of cyclin A, cyclin dependent kinase 2 (CDK2), cyclin D1, and cyclin E but down-regulated the expressions of cleaved caspase-3 and cleaved caspase-9, which was abolished by miR-28-5p inhibitor. Furthermore, luciferase reporter assay verified that miR-28-5p directly targeted MTSS1 3′UTR and down-regulated its expression. MTSS1 overexpression in TE-1 cells inhibited cell proliferation and promoted apoptosis induced by miR-28-5p mimics, whereas silencing of MTSS1 reversed cell progression induced by miR-28-5p inhibitor. We also demonstrated that miR-28-5p could promote esophageal tumor formation in vivo. Hematoxylin–eosin staining, immunohistochemistry, and TUNEL assays confirmed that miR-28-5p antagomir inhibited cell growth and accelerated apoptosis. Our results suggest that miR-28-5p may induce cell proliferation and suppress apoptosis to promote EC tumor formation via decreasing MTSS1 expression. Thus, miR-28-5p may be a potential target for human EC therapy.

Metastasis suppressor 1 acts as a tumor suppressor by inhibiting epithelial-to-mesenchymal transition in triple-negative breast cancer

Objective: This study aimed to analyze the function of metastasis suppressor 1 ( MTSS1) in triple negative breast cancer (TNBC). Methods: MTSS1 expression in 30 TNBC and paracancerous tissues was measured by quantitative reverse transcriptase polymerase chain reaction. The prognostic value of MTSS1 was assessed by Kaplan–Meier analysis followed by the log-rank test. MCF7 cells were transfected with si- MTSS1, while MDA-MB-231 cells were transfected with pcDNA3.1- MTSS1. Cell proliferation assay and transwell assay were performed to investigate the effects of MTSS1 on the biological behavior of breast cancer cells. Immunofluorescence and western blot were used to detect the influence of MTSS1 on epithelial–mesenchymal transition (EMT) markers. Results: MTSS1 expression was significantly lower in TNBC tissues compared with that in paracancerous tissues (0.012 vs. 0.370; P = 0.006). A lower MTSS1 expression level was also found in tumor tissues of patients with lymph node metastasis ( P = 0.002) or tumor node metastasis stage ( P = 0.010). Patients with low expression of MTSS1 (⩽ 0.009) had shorter disease-free survival (47.4 vs. 56.0 months; P = 0.012). The knockdown of MTSS1 in MCF7 cells inhibited cell proliferation, enhanced cell migration and invasion capacities, decreased the E-cadherin level, and increased the vimentin level, whereas overexpression of MTSS1 in MDA-MB-231 cells had the opposite effects ( P < 0.05). Conclusions: Our findings demonstrated that MTSS1 regulates proliferation, invasion, migration, and EMT in TNBC, and that decreased MTSS1 is associated with shorter disease-free survival.

Circular RNA SFMBT2 Inhibits the Proliferation and Metastasis of Glioma Cells Through Mir-182-5p/Mtss1 Pathway

Glioma is a common type of tumor in human central nervous system, and it is characterized with high mobility and mortality. The prognosis of patients with advanced glioma remains poor. Thus, it is necessary to develop novel therapeutic approaches for the treatment of this disease. Circular RNAs are a group of noncoding RNAs which have been detected in eukaryotic cells. They are tissue-specific and characterized with a more stable structure compared with linear RNAs. Recently, studies have revealed that certain circular RNAs are involved in biological processes such as gene regulation; however, the functions of most circular RNAs remain unknown and require further investigation. Furthermore, circular RNAs can act as “sponges” of its target microRNA, consequently suppressing their activity. Additionally, impaired expression of circular RNAs is reported in different diseases including cancer. In our study, low expression of circular RNA Scm like with 4 Mbt domains 2 was detected in glioma samples. Furthermore, reduced circRNA Scm like with 4 Mbt domains 2 expression was observed in human glioma cell lines compared to normal astrocyte cells. Additionally, overexpression of circRNA Scm like with 4 Mbt domains 2 suppressed the growth and metastasis of glioma cells in vitro. Moreover, microRNA-182-5p could be a downstream molecule of circRNA Scm like with 4 Mbt domains 2. The influenced of microRNA-182-5p-induced proliferation, migration, and invasion of glioma cells could be abrogated by overexpressed circRNA Scm like with 4 Mbt domains 2. In addition, metastasis suppressor 1 was predicted as a novel target of microRNA-182-5p, and its expression was restored by circRNA Scm like with 4 Mbt domains 2. In summary, our findings provided novel insight into the roles of circRNA Scm like with 4 Mbt domains 2 in glioma. More importantly, circRNA Scm like with 4 Mbt domains 2/microRNA-182-5p/metastasis suppressor 1 axis could be a putative therapeutic target for the treatment of patients with glioma.