Long non-coding RNA LINC01215 promotes epithelial-mesenchymal transition and lymph node metastasis in epithelial ovarian cancer through RUNX3 promoter methylation

Wei Liu; Shu Tan; Xiaoxu Bai; Shihong Ma; Xiuwei Chen

doi:10.1016/j.tranon.2021.101135

Long non-coding RNA LINC01215 promotes epithelial-mesenchymal transition and lymph node metastasis in epithelial ovarian cancer through RUNX3 promoter methylation

Transl Oncol. 2021 Aug;14(8):101135. doi: 10.1016/j.tranon.2021.101135. Epub 2021 May 27.

Authors

Wei Liu¹, Shu Tan², Xiaoxu Bai¹, Shihong Ma¹, Xiuwei Chen³

Affiliations

¹ Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
² Department of Gynecology Oncology, The Tumor Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China.
³ Department of Gynecology Oncology, The Tumor Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China. Electronic address: sycxrrlawst@163.com.

Abstract

Epithelial ovarian cancer (EOC) still remains the most lethal gynaecological malignancy in women, despite the recent progress in the management, including surgery and chemotherapy. According to the microarray data of the GSE18520 and GSE54388 datasets, LINC01215 was identified as an upregulated long noncoding RNA (lncRNA) in EOC. Therefore, this study aimed to figure out the involvement of LINC01215 in the progression of EOC. RT-qPCR was conducted to select the EOC cell line with the highest expression of LINC01215. Methylation of RUNX3 was then examined in EOC cells by MS-PCR. Furthermore, the interaction between LINC01215 and methylation-related proteins was revealed according to the results of RIP and RNA pull down assays. Subsequently, the involvement of LINC01215 and RUNX3 in regulating biological behaviors of EOC cells was investigated. Finally, the effects of the ectopic expression of LINC01215 and RUNX3 on the tumor formation and lymph node metastasis (LNM) of EOC cells were assessed in the xenograft tumors of nude mice. Overexpressing LINC01215 contributed to downregulated levels of RUNX3, as demonstrated by the recruitment of methylation-related proteins. Silencing of LINC01215 elevated the expression of RUNX3, thus suppressing cell proliferation, migration, invasion and EMT and decreasing the expressions of MMP-2, MMP-9 and Vimentin, but increased the expression of E-cadherin. The tumor growth and LNM were suppressed by downregulated levels of LINC01215 through inducing the expression of RUNX3. Collectively, the down-regulating LINC01215 could upregulate the expression of RUNX3 by promoting its methylation, thus suppressing EOC cell proliferation, migration and invasion, EMT, tumor growth and LNM.

Keywords: Epithelial ovarian cancer; Epithelial-mesenchymal transition; Invasion; Long non-coding RNA LINC01215; Lymph node metastasis; Metastasis; Runt-related transcription factor 3.