The miR-133b, a commonly recognized muscle-specific miRNA, was reported to be deregulated in many kinds of cancers. However, its potential roles in tumorigenesis remain greatly elusive. Herein, we demonstrate that miR-133b is significantly suppressed in human breast cancer specimens, which is reversely correlated to histological grade of the cancer. Ectopic expression of miR-133b suppresses clonogenic ability and metastasis-relevant traits in vitro, as well as carcinogenesis and pulmonary metastasis in vivo. Further studies have identified Sox9, c-MET, and WAVE2 as direct targets of miR-133b, in which Sox9 contributes to all miR-133b-endowed effects including cell proliferation, colony formation, as well as cell migration and invasion in vitro. Moreover, re-expression of Sox9 reverses miR-133b-mediated metastasis suppression in vivo. Taken together, these findings highlight an important role for miR-133b in the regulation of tumorigenesis and metastatic potential of breast cancer and suggest a potential application of miR-133b in cancer treatment.
The core-shell boronic-acid functionalized nanoparticles SnO(2)@Poly(HEMA-co-St-co-VPBA) are designed for selectively enriching glycopeptides, followed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis. Such 60 nm sized core-shell nanoparticles are prepared by means of copolymerization between 2-hydroxyethyl methacrylate (HEMA) grafted on SnO(2) nanoparticles, styrene, and 4-vinylphenylboronic acid (VPBA). All of the synthesis procedures are completed within 3 h. Cyclic boronate esters form between boronic-acid groups on the polymer chains and cis-diol groups on glycopeptides, and thus almost all intact glycopeptides from low-abundant horseradish peroxidase (HRP) and bovine asialofetuin (ASF) are enriched with high selectivity and efficiency. After enrichment, both intact N- and O-glycopeptides are characterized by multistage MS. Furthermore, we successfully apply this method to the human serum sample for characterizing the target glycoproteins haptoglobin and alpha-1-acid-glycoprotein. The present selective enriching method followed by multistage-MS analysis is proven to be a good choice for routine glycopeptide characterization.
Purpose
Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in cancer metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of an LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated.
Methods
RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling.
Results
We analyzed the RNA-seq data of MDA-MB-231 and its highly metastatic derivative MDA-MB-231-LM2 cell lines (referred to as LM2) and identified a novel lncRNA (NR_027263) named as ARHGAP5-AS1, which expression was significantly downregulated in LM2 cells. Further functional investigation showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7.
Conclusion
ARHGAP5-AS1 inhibits breast cancer cell migration via stabilization of SMAD7 protein and could serve as a novel biomarker and a potential target for breast cancer in the future.
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