Possible Role of IL-6R/STAT3/MiRNA-34a Feedback Loop in Osteosarcoma

Osteosarcoma is considered the most common primary malignant tumor that develops from the primary osteoblasts. MiRNAs are small non-coding RNAs that play a key role in tumorigenesis. The aim of this study was to detect the possible relationship between expression levels of miRNA-34a and levels of Signal transducer and activator of transcription 3 (STAT3) and interleukin-6 receptor (IL-6R) in osteosarcoma and the possible role of this relationship in development of metastases in these patients.

A total of thirty-six (36) bone samples were included in the study. They were divided into 3 groups: Group (I): Twelve normal bone samples as control group. Group (II): Twelve patients with non-metastatic osteosarcoma. Group (III): Twelve patients with metastatic osteosarcoma. MiRNA-34a expression levels were estimated using qRT-PCR. STAT3 and IL-6R levels were measured by ELISA.

Expression level of miRNA-34a was downregulated in osteosarcoma groups compared to control group. STAT3 and IL-6R levels were upregulated in osteosarcoma groups compared to control group. This difference in expression levels was found to be more significant in the metastatic group than the non-metastatic one (P<0.001 each). There was a significant positive correlation between STAT3 and IL-6R (r=0.868, P<0.001), and a significant inverse correlation between IL6 and miRNA-34a (r=-0.993, P<0.001).

miRNA-34a, STAT3 and IL-6R feedback loop could be a potential target for treatment of osteosarcoma and can be used as prognostic indicator for this disease.