Positive feedback loop SP1/MIR17HG/miR-130a-3p promotes osteosarcoma proliferation and cisplatin resistance

Yibin Meng; Dingjun Hao; Yunfei Huang; Shuaijun Jia; Jianan Zhang; Xirui He; Liang Sun; Deyin Liu

doi:10.1016/j.bbrc.2019.10.180

Positive feedback loop SP1/MIR17HG/miR-130a-3p promotes osteosarcoma proliferation and cisplatin resistance

Biochem Biophys Res Commun. 2020 Jan 15;521(3):739-745. doi: 10.1016/j.bbrc.2019.10.180. Epub 2019 Nov 6.

Authors

Yibin Meng¹, Dingjun Hao¹, Yunfei Huang¹, Shuaijun Jia¹, Jianan Zhang¹, Xirui He¹, Liang Sun², Deyin Liu³

Affiliations

¹ Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiao Tong University, Xian, Shaanxi, 710000, China.
² Department of Orthopaedic, Hong Hui Hospital, Xi'an Jiao Tong University, Xian, Shaanxi, 710000, China.
³ Department of Orthopaedic, Hong Hui Hospital, Xi'an Jiao Tong University, Xian, Shaanxi, 710000, China. Electronic address: liudeyinhonghui@126.com.

PMID: 31706574
DOI: 10.1016/j.bbrc.2019.10.180

Abstract

Long noncoding RNAs (lncRNAs) have been identified to be critical regulator in the osteosarcoma (OS) tumorigenesis. However, the role of lncRNA MIR17HG in the OS proliferation and chemotherapy resistance is still unclear. Here, this research aims to investigate the function of lncRNA MIR17HG in the OS proliferation and cisplatin resistance. Clinically, results revealed that higher MIR17HG expression was associated with shorter overall survival. Functional investigations indicated that MIR17HG promoted the proliferation, invasion and cisplatin resistance of OS cells in vitro, and the MIR17HG knockdown inhibited the growth in vivo. Mechanistically, MIR17HG targeted the miR-130a-3p/SP1 axis, moreover, transcription factor SP1 bind with the MIR17HG promoter region to promote its expression. Taken together, MIR17HG displays the tumor-promotive role in the progression of OS through SP1/MIR17HG/miR-130a-3p/SP1 feedback loop. Our findings might help us to offer novel therapeutic strategies for OS.

Keywords: Cisplatin resistance; MIR17HG; Osteosarcoma; SP1; miR-130a-3p.

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Bone Neoplasms / drug therapy*
Bone Neoplasms / genetics
Cell Line, Tumor
Cell Proliferation / drug effects
Cisplatin / pharmacology*
Cisplatin / therapeutic use
Drug Resistance, Neoplasm
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
Male
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics*
Osteosarcoma / drug therapy*
Osteosarcoma / genetics
RNA, Long Noncoding / genetics*
Sp1 Transcription Factor / genetics*

Substances

Antineoplastic Agents
MIRN130 microRNA, human
MicroRNAs
RNA, Long Noncoding
Sp1 Transcription Factor
SP1 protein, human
Cisplatin