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.
Aggrecanase-2 (ADAMTS5) is reported to play essential roles in the pathophysiology of osteoarthritis (OA). To explore the relationship between ADAMTS5 gene polymorphisms and primary OA, we conducted a community-based case-control study. A total of 732 community residents aged 40-84 years participated in the community-based study in Northeast China. After taking physical examination and radiographic examination, 420 persons of the residents were diagnosed OA (216 women and 204 men). The other 312 individuals without any symptoms of osteoarthritis or signs in the radiographs (156 women and 156 men) were considered as healthy controls. After obtaining the DNA of patients and control group, genotypes of the ADAMTS5 gene polymorphisms were determined by polymerase chain reaction (PCR) followed by restriction enzyme digestion (HAEIII for P692L in exon 7 and BSRBI for R614H in exon 5). The numbers of patients with different OA subtypes were also calculated. The genotype and allele frequency of for the exon 5C/T BSRBI polymorphism was significantly different between OA patients and control individuals (P = 0.001, OR = 0.701, 95% CI = 0.569-0.863). This difference was more obvious in cervical OA patients (P = 0.001, OR = 0.664, 95% CI = 0.521-0.847). The mutation type of exon 5C/T BSRBI polymorphism would be a protective factor for OA especially for cervical OA. Our results suggest that the ADAMTS5 gene polymorphisms may contribute to the susceptibility of osteoarthritis in the Chinese Han population.
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