Upregulated Long Non-Coding RNA LL22NC03-N64E9.1 Promotes the Proliferation and Migration of Human Breast Cancer Cells by Silencing Kruppel-Like Factor 2 Expression

Weibin Lian; Xiaohua Jiang; Liangqiang Li; Qinglan Wang; Chengye Hong; Peidong Yang; Debo Chen

doi:10.2147/CMAR.S268725

Upregulated Long Non-Coding RNA LL22NC03-N64E9.1 Promotes the Proliferation and Migration of Human Breast Cancer Cells by Silencing Kruppel-Like Factor 2 Expression

Cancer Manag Res. 2020 Oct 29:12:10763-10770. doi: 10.2147/CMAR.S268725. eCollection 2020.

Authors

Weibin Lian^#¹, Xiaohua Jiang^#², Liangqiang Li^#¹, Qinglan Wang¹, Chengye Hong¹, Peidong Yang¹, Debo Chen¹

Affiliations

¹ Department of Breast Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People's Republic of China.
² Department of Orthopedics, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, People's Republic of China.

^# Contributed equally.

Abstract

Introduction: Recently, the significant regulatory effects of lncRNAs on the oncogenesis and growth of tumor have been demonstrated by an increasing number of research projects. A previous study showed that LL22NC03-N64E9.1 could promote the development of colorectal cancer, especially via enhanced cell proliferation. Similarly, this lncRNA should have comparable functions in breast cancer (BC), which requires in-depth investigation. Therefore, this study was designed to explore the correlation of LL22NC03-N64E9.1 with BC.

Methods: qRT-PCR was used to assess the relative expression of LL22NC03-N64E9.1 in BC tissues. Cell viability examination and colony formation experiments were performed to investigate the role of LL22NC03-N64E9.1 in BC cell's proliferation. Transwell assays were used to explore the effects of LL22NC03-N64E9.1 on BC cell's migration. RNA immunoprecipitation, chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of LL22NC03-N64E9.1 with target proteins and genes in BC cells.

Results: We identified that LL22NC03-N64E9.1 is an oncogene, upregulated in BC, which was verified in a cohort of 48 pairs of BC tissues. Based on the loss-of-function experiments, silencing LL22NC03-N64E9.1 expression significantly inhibited malignancy progression. In terms of the mechanism, LL22NC03-N64E9.1 acted on the enhancer of zeste homolog 2 (EZH2) by direct binding, which promoted BC cell growth. Furthermore, in the promoters of KLF2, the trimethylation of H3K27 could be regulated by LL22NC03-N64E9.1 as the mediator.

Conclusion: Relying on the LL22NC03-N64E9.1/EZH2/KLF2 pathway, the lncRNA LL22NC03-N64E9.1 was significantly associated with BC development and could, therefore, be a potential therapeutic target to block BC growth.

Keywords: H3K27me3; KLF2; LL22NC03-N64E9.1; breast cancer; lncRNA.

Grants and funding

This study was funded by the Science and Technology Plan Project of Quanzhou (Grant No. 2018N073S) and the Startup Fund for scientific research, Fujian Medical University (Grant No. 2019QH1251).