Osteosarcoma (OS) remains one deadly disease for many affected patients. MicroRNAs (miRNAs) are thought to have an important role in tumor metastasis by regulating diverse cellular pathways. Here, we describe the function and regulation network of miR-489-3p in osteosarcoma (OS) metastasis. MiR-489-3p expression was downregulated in OS cells especially in high metastatic potential cells and was also significantly decreased in metastatic lesions compared with their corresponding primary tumor samples. Both gain- and loss-of-function studies confirmed that miR-489-3p significantly suppressed OS cell invasion and metastasis both in vitro and in vivo. Mechanistically, paired box gene 3 (PAX3) was identified as a functional target of miR-489-3p in OS cells. MiR-489-3p inhibited OS metastasis by negatively regulating expression of PAX3. In addition, PAX3 expression was markedly higher in OS tissues than in adjacent non-cancerous tissues. Transwell assays and in vivo metastasis assays demonstrated that overexpression of PAX3 significantly promoted the invasiveness and pulmonary metastasis of OS cells. On the other hand, downregulation of PAX3 markedly reduced cell metastatic potential. Mechanistic investigations indicated that prometastasis function of PAX3 was mediated by upregulating downstream target MET tyrosine kinase receptor. In conclusion, our results reveal that miR-489-3p-PAX3-MET signaling is critical to OS metastasis. Targeting the pathway described here may open new therapeutic prospects to restrict the metastatic potential of OS. © 2016 Wiley Periodicals, Inc.
Background: Computer-aided diagnosis (CAD) systems are being applied to the ultrasonographic diagnosis of malignant thyroid nodules, but it remains controversial whether the systems add any accuracy for radiologists. Objective: To determine the accuracy of CAD systems in diagnosing malignant thyroid nodules. Methods: PubMed, EMBASE, and the Cochrane Library were searched for studies on the diagnostic performance of CAD systems. The diagnostic performance was assessed by pooled sensitivity and specificity, and their accuracy was compared with that of radiologists. The present systematic review was registered in PROSPERO (CRD42019134460). Results: Nineteen studies with 4,781 thyroid nodules were included. Both the classic machine learning-and the deep learning-based CAD system had good performance in diagnosing malignant thyroid nodules (classic machine learning: sensitivity 0.86 [95% CI 0.79-0.92], specificity 0.85 [95% CI 0.77-0.91], diagnostic odds ratio (DOR) 37.41 [95% CI 24.91-56.20]; deep learning: sensitivity 0.89 [95% CI 0.81-0.93], specificity 0.84 [95% CI 0.75-0.90], DOR 40.87 [95% CI 18.13-92.13]). The diagnostic performance of the deep learning-based CAD system was comparable to that of the radiologists (sensitivity 0.87 [95% CI 0.78-0.93] vs. 0.87 [95% CI 0.85-0.89], specificity 0.85 [95% CI 0.76-0.91] vs. 0.87 [95% CI 0.81-0.91], DOR 40.12 [95% CI 15.58-103.33] vs. DOR 44.88 [95% CI 30.71-65.57]). Conclusions: The CAD systems demonstrated good performance in diagnosing malignant thyroid nodules. However, experienced radiologists may still have an advantage over CAD systems during real-time diagnosis.
Objective: Monoamine oxidase A (MAO-A) is a mitochondrial protein involved in tumourigenesis in different types of cancer. However, the biological function of MAO-A in gastric cancer development remains unknown. Methods: We examined MAO-A expression in gastric cancer tissues and in gastric cancer cell lines by immunohistochemistry and Western blot analyses. CCK8, FACS and bromodeoxyuridine incorporation assays were performed to assess the effects of MAO-A on gastric cancer cell proliferation. The role of MAO-A in mitochondrial function was determined through MitoSOX Red staining, ATP generation and glycolysis assays. Results: In the present study, we observed that MAO-A was significantly upregulated in gastric cancer tissues and in AGS and MGC803 cells. The observed MAO-A inhibition indicated decreased cell cycle progression and proliferation. Silencing MAO-A expression was associated with suppressed migration and invasion of gastric cancer cells in vitro. Moreover, alleviated mitochondrial damage in these cells was demonstrated by decreased levels of mitochondrial reactive oxygen species and increased ATP generation. MAO-A knockdown also regulated the expression of the glycolysis rate-limiting enzymes hexokinase 2 and pyruvate dehydrogenase. Finally, we observed that the glycolysis-mediated effect was weakened in AGS and MGC803 cells when MAO-A was blocked. Conclusion: The findings of the present study indicate that MAO-A is responsible for mitochondrial dysfunction and aerobic glycolysis, which in turn leads to the proliferation and metastasis of human gastric tumour cells.
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