ELK1-induced upregulation of long non-coding RNA MIR100HG predicts poor prognosis and promotes the progression of osteosarcoma by epigenetically silencing LATS1 and LATS2

被引：49

作者：

Su, Xiaochuan ^{[1
,2
]}

Teng, Junyan ^{[1
,2
]}

Jin, Guoguo ^{[3
]}

Li, Jitian ^{[3
]}

Zhao, Zhenjiang ^{[1
,2
]}

Cao, Xiangyang ^{[1
,2
]}

Guo, Yanxing ^{[1
,2
]}

Guo, Malong ^{[1
,2
]}

Li, Xiaoling ^{[1
,2
]}

Wu, Jun ^{[1
,2
]}

Wang, Chuanzhen ^{[1
,2
]}

Guo, Zhiping ^{[3
]}

Guo, Qing ^{[4
]}

机构：

[1] Henan Luoyang Orthoped Hosp, Henan Prov Orthoped Hosp, Dept Osteoarthrosis, 100 Yongping Rd, Zhengzhou 450046, Henan, Peoples R China

[2] Henan Luoyang Orthoped Hosp, Henan Prov Orthoped Hosp, Hlth Management Ctr, 100 Yongping Rd, Zhengzhou 450046, Henan, Peoples R China

[3] Henan Luoyang Orthoped Hosp, Lab Bone Tumor, 100 Yongping Rd, Zhengzhou 450046, Henan, Peoples R China

[4] Zhejiang Chinese Med Univ, 548 Bingwen Rd, Hangzhou 310053, Zhejiang, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2019年 / 109卷

关键词：

MIR100HG; ELK1; Hippo signaling pathway; Proliferation; Osteosarcoma; CELL-PROLIFERATION; GASTRIC-CANCER; LNCRNA; CARCINOMA; INVASION; TUMORIGENESIS; NATIONWIDE; MIGRATION;

D O I：

10.1016/j.biopha.2018.10.029

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Osteosarcoma (OS) is the commonest malignant bone tumor in the world. High incidence of OS has gradually become a social problem. Recent years, numerous studies have revealed that long non-coding RNAs (lncRNAs) are crucial regulators in the tumor progression. As a member of lncRNA family, MIR100HG has been reported to be an oncogene in breast cancer and acute megakaryoblastic leukemia. Nevertheless, the specific role of MIR100HG in osteosarcoma is still unclear. In this study, we investigated the biological function and molecular mechanism of MIR100HG in the progression of osteosarcoma. At first, we measured the high expression of MIR100HG in OS tissues and cell lines by qRT-PCR. Kaplan-Meier method revealed that high expression of MIR100HG is a factor for the poor prognosis of OS patients (P=0.004). To explore the effect of MIR100HG on the biological processes of OS, loss-of-function assays were conducted in OS cells. Functionally, MIR100HG knockdown suppressed cell proliferation, cell cycle progression while promoted cell apoptosis. Mechanistically, MIR100HG was upregulated by the transcription factor ELK1. The upregulation of MIR100HG led to the inactivation of Hippo pathway. Furthermore, we found that MIR100HG inactivated Hippo pathway in OS cells by epigenetically silencing LATS1 and LATS2. Rescue assays demonstrated that LATS1/2 involved in MIR100HG-mediated OS progression. In summary, our study indicated that ELK1-induced upregulation of MIR100HG promoted OS progression by epigenetically silencing LATS1 and LATS2 and inactivating Hippo pathway.

引用

页码：788 / 797

页数：10