HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2.

Extensive evidence has explored the involvement of microRNAs (miRNAs) in osteosarcoma (OS). Limitedly, the concrete function of microRNA-18b-5p (miR-18b-5p) in OS remains unexplored and largely elusive. Here, we validated that miR-18b-5p significantly elevated in OS via analyzing the data from GEO database. The results showed that miR-18b-5p was overexpressed in human OS tissues and cell lines. The clinical evidence suggested that high level of miR-18b-5p was negatively correlated with the poor prognosis of OS. Meanwhile, miR-18b-5p upregulation facilitated the proliferation and metastasis of OS cells in vitro and in vivo. The mechanism exploration demonstrated that miR-18b-5p acted as a potential inhibitor of PHF2, a tumor suppressor gene, at post-transcriptional level. Moreover, hypoxia induced gene expression of miR-18b-5p was clarified to be transcriptionally mediated by HIF-1α. The clinicopathological analysis in samples of OS patients further supported that miR-18b-5p had a positive correlation with HIF-1α expression, and negative correlation with PHF2. Collectively, the present study uncovered a new molecular mechanism of OS tumorigenesis and development and miR-18b-5p might be a prognostic biomarker and potential therapeutic target for OS treatment.

LncRNA RUSC1-AS1 promotes osteosarcoma progression through regulating the miR-340-5p and PI3K/AKT pathway.

Dysregulation of long noncoding RNA (lncRNA) is frequently involved in the progression and development of osteosarcoma. LncRNA RUSC1-AS1 is reported to be upregulated and acts as an oncogene in hepatocellular carcinoma, cervical cancer and breast cancer. However, its role in osteosarcoma has not been studied yet. In the present study, we investigated the role of RUSC1-AS1 in osteosarcoma both in vitro and in vivo. The results showed that the expression of RUSC1-AS1 was significantly upregulated in osteosarcoma cell line U2OS and HOS compared to that in human osteoblast cell line hFOB1.19. Similar results were found in human samples. Silencing RUSC1-AS1 by siRNA significantly inhibited U2OS and HOS cell proliferation and invasion, measured by CCK-8 and transwell assay. Besides, knockdown of RUSC1-AS1 increased cell apoptosis in osteosarcoma cell lines. In addition, RUSC1-AS1 promoted the epithelial-mesenchymal transition (EMT) process of osteosarcoma cells. In vivo experiments confirmed that RUSC1-AS1 knockdown had an inhibitory effect on osteosarcoma tumor growth. Mechanically, we showed that RUSC1-AS1 directly binds to and inhibits miR-340-5p and activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrated that RUSC1-AS1 promoted osteosarcoma development both in vitro and in vivo through sponging to miR-340-5p and activating the PI3K/AKT signaling pathway. Therefore, RUSC1-AS1 becomes a potential therapeutic target for osteosarcoma.

Effectiveness of montelukast for uremic pruritus in hemodialysis patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Uremic pruritus (UP) is a common and tormenting symptom in end-stage renal disease patients undergoing maintenance hemodialysis. An increasing number of studies have been published in recent years to support the effectiveness of montelukast for UP. We will conduct a comprehensive systematic review and meta-analysis to evaluate effectiveness of montelukast for UP in hemodialysis patients. METHODS: The following electronic databases were searched: Pubmed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database. The range of publication time was from the inception of the database to December 2020. Two reviewers will independently conduct article selection, data collection, and assessment of risk of bias. Any disagreement will be resolved by discussion with the third reviewer. Meta-analysis will be performed by Review Manager 5.3. The Cochrane Collaboration tool will be used to assess the risk of bias. RESULTS: This study will provide a systematic synthesis of current published data to explore the effectiveness of montelukast for UP in hemodialysis patients. CONCLUSIONS: This systematic review and meta-analysis will provide clinical evidence for the effectiveness of montelukast for UP in hemodialysis patients and inform our understanding of the value of montelukast in improving pruritus symptoms. This study will help clinicians, patients, and policy makers to make better decisions regarding the appropriate role of montelukast as a part of patient management routines. STUDY REGISTRATION NUMBER: INPLASY2020100043.

The protective role of omentin-1 in IL-1ß-induced chondrocyte senescence.

Osteoarthritis is a common type of degenerative joint disease. Inflammation-related chondrocyte senescence plays a major role in the pathogenesis of osteoarthritis. Omentin-1 is a newly identified anti-inflammatory adipokine involved in lipid metabolism. In this study, we examined the biological function of omentin-1 in cultured chondrocytes. The presence of omentin-1 potently suppresses IL-1ß-induced cellular senescence as revealed by staining with senescence-associated beta-galactosidase (SA-ß-Gal). At the cellular level, omentin-1 attenuates IL-1ß-induced G1 phase cell-cycle arrest. Mechanistically, we demonstrate that omentin-1 reduced IL-1ß-induced expression of senescent factors including caveolin-1, p21, and PAI-1 as well as p53 acetylation through ameliorating SIRT1 reduction. Notably, silencing of SIRT1 abolishes IL-1ß-induced senescence along with the induction of p21 and PAI-1, suggesting that the action of omentin-1 in chondrocytes is dependent on SIRT1. Collectively, our results revealed the molecular mechanism through which the adipokine omentin-1 exerts a beneficial effect, thereby protecting chondrocytes from senescence. Thus, omentin-1 could have clinical implication in the treatment of osteoarthritis.