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Long noncoding RNA OIP5-AS1 mediates resistance to doxorubicin by regulating miR-137-3p/PTN axis in osteosarcoma
Xingxing Sun1, Cong Tian1, Hui Zhang1
1Department of Oncology, Sixth People's Hospital East Campus Affiliated to Shanghai Jiao Tong University, Shanghai 201306, China; Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital East Campus, Shanghai 201306, China.
Abstract:
Opa-interacting protein 5 antisense RNA1 (OIP5-AS1) has been demonstrated to facilitate proliferation, metastasis and resistance to treatments in various types of cancers. Nevertheless, the exact mechanisms underlying the roles of OIP5-AS1 in osteosarcoma(OS) drug resistance have not yet been clearly elucidated. Therefore, we sought to investigate the functional involvement of OIP5-AS1 in osteosarcoma. Our results indicated that OIP5-AS1 was dramatically up-regulated in osteosarcoma drug-resistant tissues and cells in comparison with drug-sensitive tissues and cells. Also, the knockdown of OIP5-AS1 was found to have decreased doxorubicin resistance of OS cells. Further analyses revealed that OIP5-AS1 operated as a competitor for endogenous RNA of miR-137-3p as well as regulated pleiotrophin(PTN) expression, which has been reported to be an oncogene in OS in previous research. Furthermore, the loss of miR-137-3p or alternatively, the gain of PTN, both resulted in the abolishment of the inhibitory role of OIP5-AS1 silencing the proliferative activity. Our analyses indicated and helped to determine the role of OIP5-AS1 in contributing to tumorigenesis of osteosarcoma via the miR-137-3p/PTN axis and, therefore outlining its potential for use as a therapeutic target against this cancer.
Insights
Opa-interacting protein 5 antisense RNA1 (OIP5-AS1) promotes osteosarcoma (OS) drug resistance by regulating the miR-137-3p/PTN axis. Silencing OIP5-AS1 may offer a therapeutic strategy against OS.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Opa-interacting protein 5 antisense RNA1 (OIP5-AS1) is implicated in cancer progression.
- The specific role of OIP5-AS1 in osteosarcoma (OS) drug resistance remains unclear.
Purpose of the Study:
- To investigate the functional role of OIP5-AS1 in osteosarcoma.
- To elucidate the molecular mechanisms by which OIP5-AS1 influences OS drug resistance.
Main Methods:
- Quantitative real-time PCR to assess OIP5-AS1 expression in OS tissues and cells.
- Cell viability assays and doxorubicin resistance tests following OIP5-AS1 knockdown.
- RNA immunoprecipitation and luciferase reporter assays to confirm interactions between OIP5-AS1, miR-137-3p, and PTN.
Main Results:
- OIP5-AS1 expression was significantly upregulated in drug-resistant osteosarcoma tissues and cells.
- Knockdown of OIP5-AS1 decreased doxorubicin resistance in OS cells.
- OIP5-AS1 acts as a competing endogenous RNA for miR-137-3p and regulates pleiotrophin (PTN) expression, forming the miR-137-3p/PTN axis.
Conclusions:
- OIP5-AS1 contributes to osteosarcoma tumorigenesis and drug resistance through the miR-137-3p/PTN pathway.
- OIP5-AS1 represents a potential therapeutic target for overcoming drug resistance in osteosarcoma.
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