Circular RNA-lipoprotein receptor 6 (circ-LRP6) serves a role in promoting the tumorigenesis of retinoblastoma, esophageal squamous cell cancer and oral squamous cell carcinoma; however, whether circ-LRP6 demonstrates the same effect in osteosarcoma (OS) is yet to be fully elucidated.The present study aimed to analyze the expression, role and potential molecular mechanism of circ-LRP6 in OS. The expression levels of circ-LRP6, microRNA (miR)-141-3p, histone deacetylase 4 (HDAC4) and high mobility group protein 1 (HMGB1) were evaluated by reverse transcriptionquantitative PCR in OS tissues and cell lines. Cell Counting Kit-8, Transwell and Matrigel assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Western blotting was also performed to determine HDAC4 and HMGB1 protein expression levels. Bioinformatics and dual-luciferase reporter assays were used to predict and analyze the interactions between circ-LRP6 and miR-141-3p, miR-141-3p and HDAC4, as well as between miR-141-3p and HMGB1. Additionally, RNA immunoprecipitation was performed to verify the association between circ-LRP6 and miR-141-3p. The results confirmed that circ-LRP6 was highly expressed in OS tissues and cell lines. In addition, circ-LRP6 negatively regulated the expression of miR-141-3p and, in turn, miR-141-3p negatively regulated HDAC4 and HMGB1 expression. Functional assays revealed that circ-LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells, whereas the inhibition of miR-141-3p or the overexpression of either HDAC4 or HMGB1 partly reversed the inhibitory effect of circ-LRP6 knockdown. In summary, the present study determined that circ-LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells by regulating the miR-141-3p/HDAC4/HMGB1 axis.
Background This study was performed to evaluate the diagnostic and prognostic value, as well as the role of long‐chain noncoding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) in osteosarcoma (OS). Materials and Methods A quantitative real‐time polymerase chain reaction assay was to determine lncRNA CRNDE and microRNA‐335‐3p (miR‐335‐3p) expressions. The Kaplan–Meier analysis was to analyze the relationship between lncRNA CRNDE expression and survival in patients with OS. Receiver operating characteristic curves were to evaluate the diagnostic value of lncRNA CRNDE in OS. Bioinformatics analysis and luciferase reporter assays were used to predict and confirm the relationship between lncRNA CRNDE and miR‐335‐3p. Cell counting Kit‐8 and transwell migration assays assessed the role of lncRNA CRNDE and miR‐335‐3p in OS cells. Results lncRNA CRNDE expression was upregulated and miR‐355‐3p expression was downregulated in OS. In patients with OS, low lncRNA CRNDE expression demonstrated higher overall survival, whereas high lncRNA CRNDE expression was an independent poor prognostic factor. Furthermore, increased lncRNA CRNDE expression was associated with distant metastasis and the tumor‐node‐metastasis stage in patients with OS, which can be considered as an independent diagnostic biomarker in OS. We revealed that miR‐335‐3p was the target of lncRNA CRNDE. It also demonstrated that knockdown of lncRNA CRNDE inhibited OS cell proliferation, migration, and invasion, and inhibition of miR‐355‐3p promoted this effect. Finally, miR‐335‐3p partially mediated the stimulatory effects of lncRNA CRNDE in OS. Conclusion We demonstrated that lncRNA CRNDE is a potential diagnostic and prognostic biomarker for OS, and the lncRNA CRNDE/miR‐335‐3p axis participates in OS progression.
Introduction. Prosthetic joint infection (PJI) is a serious complication after arthroplasty, which results in high morbidity, prolonged treatment and considerable healthcare expenses in the absence of accurate diagnosis. In China, microbiological data on PJIs are still scarce. Hypothesis/Gap Statement. The incidence of PJI is increasing year by year, and the proportion of drug-resistant bacteria infection is nicreasing, which brings severe challenges to the treatment of infection. Aim. This study aimed to identify the pathogens in PJIs, multi-drug resistance, and evaluate the effect of the treatment regimen in patients with PJI. Methodology. A total of 366 consecutive cases of PJI in the hip or knee joint were admitted at the Orthopedic Surgery Center in Zhengzhou, China from January 2012 to December 2018. Infections were confirmed in accordance with the Infectious Diseases Society of America and the Musculoskeletal Infection Society (MSIS) criteria. Concurrently, patient demographic data, incidence and antibiotic resistance were investigated. Statistical differences were analysed using Fisher’s exact test or chi-square test. Results. Altogether, 318 PJI cases satisfying the inclusion criteria were enrolled in this study, including 148 with hip PJIs and 170 with knee PJIs. The average age of patients with hip PJIs was lesser than that of patients with knee PJIs (56.4 vs. 68.6 years). Meanwhile, coagulase-negative staphylococcus (CNS, n=81, 25.5 %) was the predominant causative pathogen, followed by Staphylococcus aureus (n=67, 21.1 %). Methicillin-resistant Staphylococcus (MRS) was identified in 28.9 % of PJI patients. In addition, fungus accounted for 4.8 % (n=15), non-tuberculosis mycobacterium accounted for 1.6 % (n=5), polymicrobial pathogens accounted for 21.7 % (n=69), and Gram-negative bacteria accounted for 7.9 % (n=25) of the total infections. The results of antibiotic susceptibility testing showed that gentamicin and clindamycin β-lactam antibiotics were poorly susceptible to Gram-positive isolates, but they were sensitive to rifampicin, linezolid and vancomycin. While antibiotics such as amikacin and imipenem were effective against Gram-negative bacteria, there was a high resistance rate of other pathogens to gentamicin, clindamycin and some quinolone antibacterial drugs. Empirical antibiotic treatment should combine vancomycin and cephalosporin, levofloxacin or clindamycin. When the pathogen is confirmed, the treatment should be individualized. Conclusions. The prevalence of culture-negative PJIs is still very high. Gram-positive bacteria are still the main type of pathogens that cause PJIs. Attention should be paid to the high incidence of MRS, such as MRSA and MR-CNS, among PJI patients. Empirical antibiotic treatment should cover Gram-positive isolates, especially Staphylococcus .
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