ABSTRACT
MicroRNAs (miRNAs) are a type of small noncoding RNAs that often play important roles in carcinogenesis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the functions and the mechanism of miR-638 in osteosarcoma (OS). The expression of miR-638 in OS and the DNA copy number of miR-638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by CCK8 assay. Different assays, including bioinformatics algorithms, luciferase report assay, and Western blotting, were used to identify the target gene proviral integration site for Moloney murine leukemia virus 1 (PIM1) of miR-638 in OS. The expression of PIM1 in clinical OS tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in OS tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in OS than in NCTs, which may induce the corresponding downregulation of miR-638 in OS. Ectopic expression of miR-638 inhibited OS cell growth in vitro. Subsequently, we identified that PIM1 is the downstream target gene of miR-638 in OS cells, and silencing PIM1 expression phenocopied the inhibitory effect of miR-638 on OS cell proliferation. Furthermore, we observed that PIM1 was overexpressed in OS tissues, and high expression of PIM1 in OS predicted poor overall survival. In summary, we revealed that miR-638 functions as a tumor suppressor through inhibiting PIM1 expression in OS.
ABSTRACT
It is stated that high expression of pyruvate kinase (PKM2) emerges as a significant player in the metabolism and progression of various human malignancies. However, the expression of PKM2 and its association with the prognosis of osteosarcoma had not yet been studied. In the present study, the expression and biological significance of PKM2 in osteosarcoma were investigated. We found that PKM2 expression was elevated in the cancerous tissues and it was more abundant than the adjacent normal tissues (60.2 vs 26.1 %, p < 0.001). Moreover, we showed that high PKM2 expression was positively correlated with Enneking stage (p = 0.006) and distant metastasis (p = 0.007) but not with the age, gender, tumor site, tumor size, histologic grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and local pain of the patients. Furthermore, Kaplan-Meier analysis revealed that the overall survival (OS) for patients with high PKM2 expression was significantly lower than those with low PKM2 expression (p < 0.001). Finally, multivariate analysis revealed that high PKM2 expression was an independent prognostic factor for osteosarcoma patients (p = 0.004). Collectively, these data indicated that elevated PKM2 might serve as a novel target for the treatment of osteosarcoma.
