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Open Access 01-12-2019 | Metastasis | Research

LincK contributes to breast tumorigenesis by promoting proliferation and epithelial-to-mesenchymal transition

Authors: Jing Li, Yajing Hao, Wenzhe Mao, Xiaowei Xue, Pengchao Xu, Lihui Liu, Jiao Yuan, Dongdong Zhang, Na Li, Hua Chen, Lin Zhao, Zhao Sun, Jianjun Luo, Runsheng Chen, Robert Chunhua Zhao

Published in: Journal of Hematology & Oncology | Issue 1/2019

Abstract

Background

Increasing evidence has demonstrated that mesenchymal stem cells (MSCs) play a role in the construction of tumor microenvironments. Co-culture between tumor cells and MSCs provides an easy and useful platform for mimicking tumor microenvironments and identifying the important members involved in tumor progress. The long non-coding RNAs (lncRNAs) have been shown to regulate different tumorigenic processes. In this study, we aimed to examine functional lncRNA deregulations associated with breast cancer malignancy instigated by MSC-MCF-7 co-culture.

Methods

The microarrays were used to profile the expression changes of lncRNAs in MCF-7 cells during epithelial-mesenchymal transition (EMT) induced by co-culture with MSCs. We found that an intergenic lncRNA KB-1732A1.1 (termed LincK, partly overlapped with GASL1) was significantly elevated. To investigate the biological function of LincK, the expression of EMT markers, cell migration, invasion, proliferation, and colony formation were evaluated in vitro and xenograft assay in nude mice were performed in vivo. Furthermore, we detected LincK expression in clinical samples using RNAscope® technology and verified aberrant expression of LincK in breast cancer data sets from The Cancer Genome Atlas (TCGA) by bioinformatic analysis. The underlying mechanisms of LincK were investigated using mRNA microarray analyses, Western blot, RNA pull down, and RNA immunoprecipitation.

Results

LincK induced an EMT progress in breast cancer cells (BCC) MCF-7, MDA-MB-453, and MDA-MB-231. The depletion of LincK decreased the growth, migration, and invasion in BCC, whereas the overexpression of LincK exerted the opposite effects. Moreover, knockdown of LincK repressed tumorigenesis, and ectopic expression of LincK promoted tumor growth in MCF-7 xenograft model. LincK ablation in MDA-MB-231 cells dramatically impaired lung metastasis when incubated intravenously into nude mice. Further, LincK was frequently elevated in breast cancer compared with normal breast tissue in clinical samples. Mechanistically, LincK may share common miRNA response elements with PBK and ZEB1 and regulate the effects of miR-200 s.

Conclusion

LincK plays a significant role in regulating EMT and tumor growth and could be a potential therapeutic target in breast cancer.

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Title: LincK contributes to breast tumorigenesis by promoting proliferation and epithelial-to-mesenchymal transition
Authors: Jing Li
Yajing Hao
Wenzhe Mao
Xiaowei Xue
Pengchao Xu
Lihui Liu
Jiao Yuan
Dongdong Zhang
Na Li
Hua Chen
Lin Zhao
Zhao Sun
Jianjun Luo
Runsheng Chen
Robert Chunhua Zhao
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Metastasis
Breast Cancer
Breast Cancer
Published in: Journal of Hematology & Oncology / Issue 1/2019
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-019-0707-8

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