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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 163 - 173 (11page)
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Purpose: This study was undertaken to explore how miR-206 represses osteosarcoma (OS) development. Materials and Methods: Expression levels of miR-206, PAX3, and MET mRNA were explored in paired OS and adjacent tissuespecimens. A patient-derived OS cell line was established. miR-206 overexpression and knockdown were achieved by lentiviraltransduction. PAX3 and MET overexpression were achieved by plasmid transfection. Treatment with hepatocyte growth factor(HGF) was utilized to activate c-Met receptor. Associations between miR-206 and PAX3 or MET mRNA in OS cells were verifiedby AGO2-RNA immunoprecipitation assay and miRNA pulldown assay. OS cell malignancy was evaluated in vitro by cell proliferation,metastasis, and apoptosis assays. PAX3 and MET gene expression in OS cells was assayed by RT-qPCR and Western blot. Activation of PI3K-AKT and MAPK-ERK in OS cells were assayed by evaluating Akt1 Ser473 phosphorylation and total threoninephosphorylation of Erk1/2, respectively. Results: Expression levels of miR-206 were significantly decreased in OS tissue specimens, compared to adjacent counterparts,and were inversely correlated with expression of PAX3 and MET mRNA. miR-206 directly interacted with PAX3 and MET mRNAin OS cells. miR-206 overexpression significantly reduced PAX3 and MET gene expression in OS cells in vitro, resulting in significantdecreases in Akt1 and Erk1/2 activation, cell proliferation, and metastasis, as well as increases in cell apoptosis, while miR-206 knockdown showed the opposite effects. The effects of miR-206 overexpression on OS cells were reversed by PAX3 or METoverexpression, but only partially attenuated by HGF treatment. Conclusion: miR-206 reduces OS cell malignancy in vitro by targeting PAX3 and MET gene expression.
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참고문헌 (29)
참고문헌 신청
Gianferante DM / 2017 / Germline and somatic genetics of osteosarcoma-connecting aetiology, biology and therapy / Nat Rev Endocrinol 13:480~491
Gill J / 2013 / New targets and approaches in osteosarcoma / Pharmacol Ther 137:89~99
Kansara M / 2014 / Translational biology of osteosarcoma / Nat Rev Cancer 14:722~735
Ritter J / 2010 / Osteosarcoma / Ann Oncol 21(Suppl 7):vii320~325
Iwakawa HO / 2015 / The functions of microRNAs : mRNA decay and translational repression / Trends Cell Biol 25:651~665
Gill J / 2013 / New targets and approaches in osteosarcoma / Pharmacol Ther 137:89~99
Kansara M / 2014 / Translational biology of osteosarcoma / Nat Rev Cancer 14:722~735
Ritter J / 2010 / Osteosarcoma / Ann Oncol 21(Suppl 7):vii320~325
Iwakawa HO / 2015 / The functions of microRNAs : mRNA decay and translational repression / Trends Cell Biol 25:651~665
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