Long non-coding RNA LINC00161 sensitises osteosarcoma cells to cisplatin-induced apoptosis by regulating the miR-645-IFIT2 axis.
Chemotherapeutic insensitivity remains a major obstacle to osteosarcoma treatment. Recently, increasing evidence has suggested that long non-coding RNAs (lncRNAs) play an essential role in tumourigenesis. However, the potential biological roles and regulatory mechanisms of novel lncRNAs in response to cisplatin treatment are poorly understood. Here, we found that lncRNA LINC00161 was induced by cisplatin in osteosarcoma cells. Elevated LINC00161 increased cisplatin-induced apoptosis and reversed the cisplatin-resistant phenotype of osteosarcoma cells by upregulating IFIT2. Further mechanistic studies revealed that LINC00161 could sponge endogenous miR-645 and inhibit its activity leading to IFIT2 increase. In addition, we identified that LINC00161 enhanced cisplatin-induced apoptosis through regulation of the miR-645-IFIT2 pathway. Thus, these findings demonstrate that LINC00161 is an essential regulator in cisplatin-induced apoptosis, and the LINC00161-miR-645-IFIT2 signalling axis plays an important role in reducing osteosarcoma chemoresistance.
Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
Yuan
Y
Wang
Laboratory of Pathogenic Biology, College of Basic Medical Science of Dalian Medical University, Dalian 116027, China.
Li
L
Zhang
Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
Xifu
X
Zheng
Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
Weiliang
W
Zhong
Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
Xiliang
X
Tian
Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
Baosheng
B
Yin
Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
Kang
K
Tian
Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China. Electronic address: drzweiguo@163.com.
Weiguo
W
Zhang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C484289:IFIT2 protein, human; C000598122:MIRN645 microRNA, human; D035683:MicroRNAs; D011506:Proteins; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; C000621547:long non-coding RNA LINC00161, human; D002945:Cisplatin
Apoptosis; Chemoresistance; IFIT2; LINC00161; Long non-coding RNA