Background: Recently, dysregulation of lncRNA SNHG12 has been determined in kinds of cancers. However, definite prognostic value of SNHG12 remains unclear. We conducted this meta-analysis to evaluate the association between SNHG12 expression levels and caner prognosis.Methods: A literature retrieval was conducted by searching kinds of databases. The meta-analysis of prognostic and clinicopathological parameters was performed by using Revman 5.2 and Stata 12.0 software. Besides, The Cancer Genome Atlas dataset was analyzed to validate the results in our meta-analysis via using Gene Expression Profiling Interactive Analysis.Results: High SNHG12 expression significantly predicted worse overall survival (HR=1.97, 95%CI 1.56-2.48, P<0.01) and recurrence-free survival (HR=1.71, 95%CI 1.05-2.78, P<0.01). Tumor type, sample size, survival analysis method, and cut-off value did not alter SNHG12 prognosis value according to stratified analysis results. Additionally, patients with elevated SNHG12 expression were more prone to unfavorable clinicopathological outcomes, including larger tumor size, lymph node metastasis, distant metastasis, advanced clinical stage. Online cross-validation in TCGA dataset further proved that cancer patients with upregulated SNHG12 expression had worse overall survival and disease-free survival.Conclusion: Elevated SNHG12 expression was associated with poor survival and unfavorable clinicopathological features in various cancers, and therefore might be a potential prognostic biomarker in human cancers.
Background This study probes into the function and mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosomes loaded with miR-150-5p in mechanical allodynia. Methods BMSCs were infected with miR-150-5p inhibition lentiviruses to obtain exosomes with low miR-150-5p expression. A L5 spinal nerve ligation (SNL) model was established in rats where exosomes, NOTCH2 overexpression/inhibition plasmids, or microglial cells were intrathecally administered. Hind paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of rats were measured. TUNEL staining was used to measure the apoptotic rate in rat spinal dorsal horn (SDH), ELISA to evaluate pro-inflammatory factor levels, and RT-qPCR, western blotting, and immunohistochemistry to detect miR-150-5p and NOTCH2 expression. Immunofluorescence was used for localizing exosomes and NOTCH2 and detecting the expression of OX42, a maker for microglia. Dual luciferase reporter and RNA pull down assays were performed to validate the putative binding between miR-150-5p and NOTCH2. Results NOTCH2 expressed at a high level and miR-150-5p was downregulated in SDH of SNL rats. Exosomes injected were localized in rat SDH. BMSC-exosomes or NOTCH2 downregulation increased PWT and PWL of SNL rats and reduced apoptosis and inflammation in SDH. In contrast, NOTCH2 overexpression aggravated mechanical allodynia and SDH injury. Moreover, inhibiting miR-150-5p in BMSC-exosomes offset the therapeutic effects of BMSC-exosomes. Microglia activation induced mechanical allodynia in wild rats, while intrathecal injection of microglial cells incubated with BMSC-exosomes showed alleviated mechanical allodynia in SNL rats. NOTCH2 was targeted by miR-150-5p. Conclusion BMSC-derived exosomal miR-150-5p alleviates mechanical allodynia by targeting NOTCH2 in microglial cells.
Denosumab is a monoclonal antibody that targets and inhibits the osteoclast activating factor receptor activator for nuclear factor-κB ligand (RANKL). It has been widely used in the treatment of osteoporosis, giant cell tumors of bone, and in the prevention of malignant skeletal-related events (SREs). We collected the research results and related MeSH terms of denosumab from 2011 to 2021 through the Web of Science and PubMed, respectively. The literature was visualized and analyzed by CiteSpace and bibliometric online analysis platforms. The MeSH terms were biclustered using the Bibliographic Co-Occurrence Analysis System (BICOMB) and graph clustering toolkit (gCLUTO). The results show that the number of denosumab-related annual publications had increased from 51 to 215, with the United States leading and Amgen Inc. being the most influential in the past 10 years. Articles published in the Journal of Bone and Mineral Research had the highest total citations. Three scholars from Shinshu University in Matsumoto, Yukio Nakamura, Takako Suzuki, and Hiroyuki Kato, joined the field relatively late but produced the most. The clinical comparison and combination of denosumab with other drugs in the treatment of osteoporosis was the most significant focus of research. Drug withdrawal rebound and management strategies have gained more attention and controversy recently. MeSH analysis revealed eight major categories of research hotspots. Among them, exploring the multiple roles of the RANK-RANKL-OPG system in tumor progression, metastasis, and other diseases is the potential direction of future mechanism research. It is a valuable surgical topic to optimize the perioperative drug administration strategy for internal spinal fixation and orthopedic prosthesis implantation. Taken together, the advantages of denosumab were broad and cost-effective. However, there were still problems such as osteonecrosis of the jaw, severe hypocalcemia, a high recurrence rate of giant cells in the treatment of bone and individual sarcoidosis, and atypical femoral fractures, which need to be adequately solved.
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