MicroRNAs have emerged as fundamental regulators in gene expression through silencing gene expression at the post-transcriptional and translational levels. Osteosarcoma is the most common type of primary malignant bone tumor and is characterized by complex genetic changes and resistance to conventional treatments. In our study, the role of miR-33b in the progression and metastasis of osteosarcoma was investigated. Our results showed that miR-33b was significantly downregulated in osteosarcoma tissue and cell lines. Overexpression of miR-33b significantly inhibited cell proliferation, migration, and invasion in the MG-63 osteosarcoma cell line. Moreover, we also showed that c-Myc was negatively regulated by miR-33b at the posttranscriptional level, via a specific target site within the 3′UTR. Overexpression of c-Myc impaired miR-33b-induced inhibition of proliferation and invasion in osteosarcoma cells. The expression of c-Myc was frequently downregulated in osteosarcoma tumors and cell lines and was inversely correlated with miR-33b expression. Thus, our findings suggest that miR-33b inhibits osteosarcoma cells migration and invasion by targeting the c-Myc gene, acting as tumor suppressor. The findings of this study contribute to current understanding of the functions of miR-33b in osteosarcoma.
Background:Parkinson disease (PD) is a neurodegenerative disease characterized by chronic and progressive loss of dopaminergic neurons in substansia nigra pars compacta. Oxidative stress is proposed to play a critical role in the pathogenesis of PD. Uric acid (UA), as an important physiological antioxidant, is identified a molecular predictor associated with a decreased risk and a slower disease progression for PD and potential neuroprotectant of PD by increasing epidemiological and clinical evidences. Within this review, we will present a comprehensive overview of the data linking UA to PD in recent years.Methods:We searched PubMed, EMBASE, Web of Science databases for relevant studies. Any observational or experimental studies that evaluated UA and PD were our goal of searching the electric databases.Results:Twelve studies that evaluated UA and PD were identified in this review. We reviewed the roles of UA in the pathogenesis of PD, the association of UA with morbidity, severity/progression, nonmotor symptoms, motor complications of PD, with an attempt to provide new ideas for diagnosis and treatment in PD.Conclusion:Our findings supported that lots of clinical and epidemiological data observed lower UA levels in PD patients. Manipulation of UA or its precursors’ concentration could be effective to treat or prevent PD. However, it is still suspectable that higher UA levels are better enough to PD patients. Furthermore, for the complex nature of PD and its heterogeneous genetic and environmental influences, it is inadequate for just manipulating UA in treating the disease.
Background
This study aimed to evaluate the association of circular RNA La‐related RNA‐binding protein 4 (circ‐LARP4) with clinical features and prognosis in osteosarcoma patients, and further explore its effect on chemosensitivity in osteosarcoma cells.
Methods
Seventy‐two osteosarcoma patients with Enneking stage IIA‐IIB who underwent resection were consecutively enrolled, and then, tumor tissues and non‐tumor tissues were obtained. Circ‐LARP4 in tumor tissue/non‐tumor tissue was detected by quantitative polymerase chain reaction. After circ‐LARP4 overexpression and negative control overexpression plasmid transfection, relative cell viability (%) was evaluated by Cell Counting Kit‐8 in MG63 cells treated by different concentrations of cisplatin, methotrexate, and doxorubicin, and IC50 was calculated.
Results
Circ‐LARP4 was downregulated in tumor tissue compared with non‐tumor tissue and had a good value in distinguishing tumor tissue from non‐tumor tissue with an area under curve of 0.829 (95% CI: 0.762‐0.859). Meanwhile, tumor circ‐LARP4 was negatively correlated with the Enneking stage. After resection, circ‐LARP4 high expression patients showed an increased tumor cell necrosis rate to adjuvant chemotherapy compared to circ‐LARP4 low expression patients, and circ‐LARP4 high expression correlated with prolonged disease‐free survival and overall survival. In vitro experiments revealed that circ‐LARP4 overexpression elevated the chemosensitivity of MG63 cells to cisplatin and doxorubicin but not methotrexate, with decreased cisplatin IC50 and doxorubicin IC50 concentrations than negative control. Besides, miR‐424 overexpression attenuated the chemosensitivity in circ‐LARP4 overexpression‐treated MG63 cells.
Conclusion
Circ‐LARP4 high expression correlates with decreased Enneking stage and prolonged survival profiles, and it elevates chemosensitivity to cisplatin and doxorubicin via sponging miR‐424 in osteosarcoma.
DECT showed relatively high sensitivity and specificity in the diagnosis of gout. Synthetically considering these DECT abnormalities could improve the diagnostic sensitivity. More rigorous and standardized studies are still needed to support these findings.
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