A causal role for circulating miR-34b in osteosarcoma

PurposeTo investigate the associations between plasma miR-34b/c expression levels and osteosarcoma (OS).Subjects and methodsA case-control study was conducted in 133 patients with OS and 133 controls. MiR-34b/c levels were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays. Genotyping of SNP rs4938723 was done using the TaqMan assay. The causal association was examined by mendelian randomization analysis.ResultsPlasma miR-34b level was significantly lower in OS patients than in controls (P = 0.001). Expression levels of miR-34b in OS tissues decreased (P = 3.22 × 10−4) and was significantly related with its expression in plasma (r = 0.21, P = 0.004). Compared with wild-type TT genotype, the variant genotypes of rs4938723 TC/CC were significantly associated with increased OS risk (TC vs. TT: OR, 1.97 [95% CI: 1.40–2.55], P = 0.021; CC vs. TT: OR, 2.76 [95% CI: 2.00–3.53], P = 0.009; TC + CC vs. TT: OR, 2.16 [95% CI: 1.61–2.70], P = 0.006), consistent with its decreased effect on plasma miR-34b (TC vs. TT: −0.32 (−0.43, −0.21), P < 0.001; CC vs. TT: −0.70 (−0.84, −0.56), P < 0.001; TC + CC vs. TT: −0.42 (−0.53, −0.32), P < 0.001). Adjustment for miR-34b completely abolished the association between SNP rs4938723 and OS risk (P > 0.05). In addition, plasma expression levels of miR-34b were significantly decreased in the metastatic patients compared with that in the non-metastatic ones (P = 0.004).ConclusionPlasma miR-34b was causally associated with OS risk and related with its metastatic status, suggesting that plasma miR-34b might be a novel biomarker and a potential treatment target for OS.