Knockdown of KCNQ1OT1 Suppresses Cell Invasion and Sensitizes Osteosarcoma Cells to CDDP by Upregulating DNMT1-Mediated Kcnq1 Expression

Xu Qi; Xiao-Jun Yu; Xu-Ming Wang; Tie-Nan Song; Jie Zhang; Xin-Zhen Guo; Guo-Jun Li; Ming Shao

doi:10.1016/j.omtn.2019.06.010

Knockdown of KCNQ1OT1 Suppresses Cell Invasion and Sensitizes Osteosarcoma Cells to CDDP by Upregulating DNMT1-Mediated Kcnq1 Expression

Mol Ther Nucleic Acids. 2019 Sep 6:17:804-818. doi: 10.1016/j.omtn.2019.06.010. Epub 2019 Jun 27.

Authors

Xu Qi¹, Xiao-Jun Yu², Xu-Ming Wang², Tie-Nan Song², Jie Zhang², Xin-Zhen Guo², Guo-Jun Li², Ming Shao³

Affiliations

¹ Department of Neurology, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, P.R. China.
² The 1st Department of Orthopedics, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, P.R. China.
³ The 1st Department of Orthopedics, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, P.R. China. Electronic address: shaoming6@yeah.net.

Abstract

Osteosarcoma is a malignant bone tumor, with a high incidence worldwide. The involvement of long non-coding RNAs (lncRNAs) in cancers and their molecular association with the progression of osteosarcoma have been previously discussed. We conducted the present study to examine the effect of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) on osteosarcoma cell invasion and chemosensitivity to cisplatin (CDDP). After determination of the expression of Kcnq1 in osteosarcoma tissues and cells, the plasmids with overexpression or knockdown KCNQ1OT1 were introduced into the cells to aid the identification of cell proliferation, migration, invasion, chemosensitivity to CDDP, and apoptosis. Then, the interaction between KCNQ1OT1 and the Kcnq1/DNA methyltransferase 1 (DNMT1) axis was evaluated by measuring the level of Kcnq1 promoter region methylation and DNMT1 enrichment of the Kcnq1 promoter region. Low Kcnq1 expression and high KCNQ1OT1 expression were shown in osteosarcoma tissues and cells. Kcnq1 was negatively mediated by KCNQ1OT1 via DNMT1. The overexpression of Kcnq1 or knockdown of KCNQ1OT1 inhibited the proliferation, migration, and invasion, and it promoted the chemosensitivity to CDDP and apoptosis of MG-63 cells and its CDDP-resistant cell lines. Moreover, the same trend was observed in the cells following methylation inhibitor treatment. Collectively, knockdown of KCNQ1OT1 can inhibit the osteosarcoma progression through the Kcnq1/DNMT1 axis.

Keywords: DNA methyltransferase 1; Kcnq1; chemosensitivity to cisplatin; long non-coding RNA KCNQ1; osteosarcoma.

Publication types

Retracted Publication