Long noncoding RNA OIP5-AS1 mediates resistance to doxorubicin by regulating miR-137-3p/PTN axis in osteosarcoma

• Published in: Biomedicine & pharmacotherapy 2020-08, Vol.128, p.110201-110201, Article 110201
• Main Authors: Sun, Xingxing, Tian, Cong, Zhang, Hui, Han, Kun, Zhou, Meixiang, Gan, Zhihua, Zhu, Hongling, Min, Daliu
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - pharmacology; Apoptosis - drug effects; Bone Neoplasms - drug therapy; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line, Tumor; Chemoresistance; Cytokines - genetics; Cytokines - metabolism; Doxorubicin - pharmacology; Drug Resistance, Neoplasm - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; lncRNAOIP5-AS1; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; miR-137-3p; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - genetics; Osteosarcoma - metabolism; Osteosarcoma - pathology; Pleiotrophin; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Tumor Burden - drug effects; Xenograft Model Antitumor Assays
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.110201

[Display omitted] •lncRNA OIP5-AS1 was significantly upregulated in OS chemo-resistant tissues and cell lines. Knockdown of OIP5-AS1 reduced doxorubicin resistance in OS in vitro and in vivo.•miR-137-3p was significantly downregulated in OS chemo-resistant tissues and cell lines; overexpression of miR-137-3p decreased doxorubicin resistance in OS.•OIP5-AS1 negatively regulated miR-137-3p expression; miR-137-3p negatively regulated PTN expression; OIP5-AS1 positively regulated PTN expression.•lncRNA OIP5-AS1 mediates resistance to doxorubicin by regulating miR-137-3p/PTN axis in osteosarcoma. 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.