A causal role for circulating miR-34b in osteosarcoma.
OBJECTIVE
To investigate the associations between plasma miR-34b/c expression levels and osteosarcoma (OS).


METHODS
A 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.


RESULTS
Plasma 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).


CONCLUSIONS
Plasma 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.
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
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Q
Tian
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
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J
Jia
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
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S
Ling
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: YongLiuabc@163.com.
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Y
Liu
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
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S
Yang
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
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Z
Shao
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D012516:Osteosarcoma / Q000097:blood / Q000235:genetics* / Q000556:secondary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D055815:Young Adult
D014408:Biomarkers, Tumor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs
Osteosarcoma; SNPs; miRNA-34b