RESUMO
Long non-coding RNAs (lncRNA) have been identified as key regulators of tumorigenesis and development. We aim to explore the biological functions and molecular mechanisms of lncRNA MIR200CHG in breast cancer. We found that MIR200CHG is highly expressed in breast cancer tissues and is related to the tumor size and histopathological grade. In vitro and in vivo experiments confirmed that MIR200CHG can promote breast cancer proliferation, invasion, and drug resistance. MIR200CHG directly binds to the transcription factor Y-box binding protein-1 (YB-1), and inhibits its ubiquitination and degradation. MIR200CHG regulates YB-1 phosphorylation at serine 102, thereby affecting the expression of genes related to tumor cell proliferation, apoptosis, invasion, and drug resistance. Additionally, MIR200CHG partially affects the expression of miR-200c/141-3p encoded by its intron region. Therefore, MIR200CHG can promote the proliferation, invasion, and drug resistance of breast cancer by interacting with and stabilizing YB-1, and has the potential to become a target for breast cancer treatment.
RESUMO
tRNA-derived fragments offer a recently identified group of non-coding single-stranded RNAs that are often as abundant as microRNAs in cancer cells and play important roles in carcinogenesis. However, the biological functions of them in breast cancer are still unclear. Hence, we focused on investigating whether tiRNAs could play a key role in the progression of breast cancer. We have identified 5'-tiRNAVal with significantly low expression in breast cancer tissues. The down-regulation of serum 5'-tiRNAVal was positively correlated with stage progression and lymph node metastasis. Overexpression of 5'-tiRNAVal suppressed cells malignant activities. FZD3 was confirmed to be a direct target of 5'-tiRNAVal in breast cancer. In addition, FZD3, ß-Catenin, c-myc and cyclinD1 levels in 5'-tiRNAVal overexpressing cells were downregulated while APC was inversely upregulated. Moreover, 5'-tiRNAVal inhibited the FZD3-mediated Wnt/ß-Catenin signaling pathway in breast cancer cells. Finally, 5'-tiRNAVal levels differentiated breast cancer from healthy controls with a sensitivity of 90.0% and specificity of 62.7%. This is the first study to show that 5'-tiRNAVal as a new tumor-suppressor through inhibition of FZD3/Wnt/ß-Catenin signaling pathway, which could be as a potential diagnostic biomarker for breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Receptores Frizzled/metabolismo , RNA de Transferência de Valina/metabolismo , Via de Sinalização Wnt , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Regulação para Baixo , Feminino , Receptores Frizzled/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Células MCF-7 , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA de Transferência de Valina/genética , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Recent studies have shown that expression of metastasis-associated in colon cancer-1(MACC1) is observed in different types of cancer and plays an important role in tumor metastasis. However, the expression of MACC1 and its possible role in esophageal cancer remains unknown. In this study, we determined the expression of MACC1 in esophageal cancer by utilizing immunohistochemistry and analyzed the relationship between the expression and esophageal cancer prognosis. Immunohistochemistry results showed that 47 of 85 cancer lesions (55.2 %) were stained positive, and high expression of MACC1 was correlated with the node metastasis and TNM stage (P < 0.05). The Kaplan-Meier survival curve showed that patients with high MACC1 expression had significantly reduced overall 5-year survival rates (P = 0.004). Cox regression analysis revealed that high expression of MACC1 was associated with increased risk of death (hazard ratio [HR] =2.25) in patients with esophageal cancer. These findings suggested that high expression of MACC1 was correlated with progression and metastasis of esophageal cancer and might serve as a novel prognostic marker for patients with esophageal cancer.
