Background Circular RNAs (circRNAs) have been shown to participate in the chemoresistance and tumorigenesis of multiple cancers. The purpose of this research was to investigate the function of circ_0081001 in methotrexate (MTX) resistance of osteosarcoma (OS) and its potential molecular mechanism. Methods The expression of circ_0081001, cytochrome P450 family 51 subfamily A member 1 (CYP51A1), and miR-494-3p was detected by qRT-PCR. Cell viability, apoptosis, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay, respectively. Western blot (WB) assay was used to measure the protein levels of cleaved-caspase3 (cleaved-casp3), E-cadherin, N-cadherin, and transglutaminase-2 (TGM2). The interaction between miR-494-3p and circ_0081001 or TGM2 was predicted by bioinformatics analysis and verified using the dual-luciferase reporter assay. The mice xenograft model was established to investigate the roles of circ_0081001 in MTX resistance of OS in vivo. Results Circ_0081001 and TGM2 were upregulated, and miR-494-3p was downregulated in MTX-resistant OS tissues and cells. Moreover, circ_0081001 interference enhanced cell sensitivity to MTX through promoting apoptosis and inhibiting cell viability and metastasis in vitro. Furthermore, circ_0081001 was identified as a molecular sponge of miR-494-3p to upregulate TGM2 level. In addition, circ_0081001 knockdown inhibited MTX resistance via upregulating miR-494-3p and downregulating TGM2. Besides, circ_0081001 downregulation improved MTX sensitivity of OS in vivo. Conclusion Knockdown of circ_0081001 enhanced MTX sensitivity of OS cells through downregulating TGM2 by sponging miR-494-3p, elucidating a novel regulatory mechanism for chemoresistance of OS and providing a potential circRNA-targeted therapy for OS.
Hook plate treatment for AC joint dislocation can achieve the desired results, but the efficacy was significantly different depending on the different angles of the hook plate. AHP should be controlled within the range of 0-40° as much as possible when making clinical decisions.
Circular RNA sterile alpha motif domain containing 4A (circSAMD4A) was found to be differentially expressed in osteosarcoma and contributed to the tumorigenesis of osteosarcoma. However, the role of circSAMD4A in doxorubicin (DXR) resistance of osteosarcoma is yet to be elucidated. Levels of circSAMD4A, microRNA (miR)-218-5p and Krüppel-like factor 8 (KLF8) were detected using quantitative reverse transcription-polymerase chain reaction. Western blot was applied to detect the protein levels of KLF8, cyclin D1 and p21. Cell viability, cell cycle, migration and invasion were analyzed using Cell Counting Kit-8 assay, flow cytometry and transwell assay, respectively. The interaction between miR-218-5p and circSAMD4A or KLF8 was verified using dual-luciferase reporter assay or RNA immunoprecipitation assay. In vivo experiments were performed using murine xenograft models. CircSAMD4A and KLF8 were elevated in osteosarcoma, and knockdown of circSAMD4A or KLF8 sensitized osteosarcoma cells to DXR by mediating resistant cell viability, migration and invasion inhibition, and cell cycle arrest in vitro. miR-218-5p was decreased in osteosarcoma, and miR-218-5p inhibition enhanced DXR resistance. Besides, miR-218-5p was found to bind to circSAMD4A or KLF8, and subsequent rescue experiments indicated that miR-218-5p inhibition reversed the inhibitory effects of circSAMD4A silencing on DXR resistance, and silencing miR-218-5p enhanced DXR resistance by targeting KLF8 in osteosarcoma cells. Moreover, circSAMD4A could indirectly regulate KLF8 via miR-218-5p. Additionally, circSAMD4A knockdown enhanced the cytotoxicity of DXR in osteosarcoma in vivo via regulating miR-218-5p and KLF8. In all, circSAMD4A enhanced cell DXR resistance in osteosarcoma by regulating the miR-218-5p/KLF8 axis, suggesting a novel therapeutic target for therapy-resistant osteosarcoma.
Background Disc degeneration is characterized partly by the degradation in the extracellular matrix (ECM) and excess apoptosis of nucleus pulposus (NP) cells. NLRX1 (nucleotide-binding, leucine-rich repeat containing X1) is different from the other nucleotide-binding-domain and leucine-rich-repeat proteins and mainly located to the mitochondrial. It negatively regulates NF-κB (nuclear factor kappa B) and apoptosis inhibition. However, how NLRX1 is regulated and exerts effects in disc degeneration is unclear. Thus, the study aimed to analyze the effects of NLRX1 on NP cells. Material/Methods NLRX1 expression was detected in interleukin (IL)-1β-induced NP cells by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Then, NLRX1 was overexpressed in IL-1β-induced NP cells to detect apoptosis-related proteins and the extracellular matrix (ECM) by western blot, along with the detection of apoptosis levels using flow cytometry. StarBase predicted miR-423-5p target 3′UTR of NLRX1. Dual luciferase reporter assay showed that miR-423-5p could bind to the 3′UTR of NLRX1. Besides, miR-423-5p significantly affected NLRX1 levels detected by qRT-qPCR. Results The miR-423-5p overexpression markedly, and negatively regulated the protective effects of NLRX1 on IL-1β induced NP cells. Thus, our results suggested that miR-423-5p mediated the regulation of NLRX1 to affect apoptosis and ECM levels in IL-1β induced NP cells. Conclusions miR-423-5p and NLRX1 could be potential therapeutic targets for patients with disc degeneration.
HighlightsThis report describes a case of a Popliteal pseudoaneurysm and arteriovenous fistula after Arthroscopic anterior and Posterior Cruciate Ligament Reconstruction.An 57-year-old male who complained of pain and swelling around the left lower extremity after the ACL and PCL reconstruction using a semitendinosus graft from the two limbs caused by bicycle accident.He was diagnosed with the popliteal pseudoaneurysm and arteriovenous fistula by the Doppler ultrasonographic examination and CTA,and transferred to the interventional radiology suite where a successful vascular stent implantation was made. There was no postoperative complication.Vascular injury is a very rare complication of knee surgery, but surgeons should always consider this possibility in patients who have undergone knee arthroscopy.If the patient has symptoms of pain in the popliteal area and unexplainable swelling following arthroscopic ACL and PCL reconstruction, a popliteal vascular injury should be suspected.In order to minimize the risk of vascular complications in ACL and PCL reconstructive surgery, we advise to look for less traumatizing instruments and to limit the amount of riskful actions, precise attention should be paid in the establishment of the femoral tunnels.
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