期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 234, 期 5, 页码 6927-6939出版社
WILEY
DOI: 10.1002/jcp.27435
关键词
chemoresistance; FN1; lncRNA OIP5-AS1; miR-200b-3p; osteosarcoma
资金
- National Natural Science Foundation of China [81572630]
- Fundamental Research Funds for the Central Universities [22120170216]
- Shanghai Pujiang Program of Shanghai Science and Technology Commission [13PJD023]
- Shanghai Jiaotong University Medical-Engineering Cross Research Fund [YG2012MS49]
Chemoresistance has been an obstacle in the further improvement of 5-year survival rates of osteosarcoma (OS) patients, but the underlying mechanism of chemo-resistance remains unclear. A comprehensive analysis of mRNAs and noncoding RNAs related to OS chemo-resistance could help solve this problem. In the current study, we first identified that fibronectin-1 (FN1), screened by microarray analysis in three paired chemo-resistant and chemo-sensitive OS cell lines, was significantly upregulated in the chemo-resistant OS cell lines and tissues and was related to unfavourable prognosis. Further functional assays revealed that FN1 inhibition greatly increased the sensitivity of OS cells to doxorubicin in vitro and in vivo, whereas FN1 overexpression had the opposite effect. Moreover, mechanistic investigation demonstrated, by a series of assays that included luciferase reporter gene, RNA immunoprecipitation, RNA pull-down and rescue assays, that FN1 expression was regulated by the oncogenic long noncoding RNA (lncRNA) OIP5-AS1 through sponging miR-200b-3p. Thus, these results indicated the role and potential application of the lncRNA OIP5-AS1/miR-200b-3p/FN1 regulatory pathway as a promising target in treatment of OS chemo-resistance.
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