LncRNA ST8SIA6-AS1 promotes proliferation, migration and invasion in breast cancer through the p38 MAPK signalling pathway

Author:

Fang Kai1,Hu Caixia1,Zhang Xiufen1,Hou Yafei2,Gao Danfeng1,Guo Zijian3,Li Lihua1

Affiliation:

1. Department of Oncology Institute, The Affiliated Hospital of Jiangnan University, Wuxi, China

2. Department of Immunology, Institute of Immunology, School of Medicine, Shanghai Jiaotong University, Shanghai, China

3. Department of Oncological Surgery, The Affiliated Hospital of Jiangnan University, Wuxi, China

Abstract

Abstract Long non-coding RNAs (lncRNAs) are regarded as important functional regulators of various biological processes and are also known to be involved in the occurrence and development of human cancers, including breast cancer (BC). In our present study, the RNA expression profiling data for a large cohort of human BC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the differentially expressed lncRNAs were screened out. We found that the expression of ST8SIA6-AS1 was elevated in BC tumour tissues compared with the adjacent normal tissues in the samples from the TCGA and GEO datasets, as well as in 138 BC tissue samples obtained by us. The high expression of ST8SIA6-AS1 was associated with estrogen receptor-negative, progesterone receptor-negative, advanced tumour-node-metastasis stage and worse survival in BC patients. In vitro functional studies revealed that high expression of ST8SIA6-AS1 promoted proliferation, invasion and migration of BC cell lines. The results of the in vivo studies indicated that upregulation of ST8SIA6-AS1 promoted xenograft tumour growth of BC. Mechanistically, ST8SIA6-AS1 regulated AKT1 and p38 mitogen-activated protein kinase (MAPK) gene expression by affecting their mRNA and protein levels, respectively, and it also affected the phosphorylation of AKT1 protein. Rescue experiments indicated that ST8SIA6-AS1 promoted BC cell proliferation, invasion and migration in a p38 MAPK signalling-mediated manner. Together, our data suggest that ST8SIA6-AS1 plays an important role in the occurrence and development of BC and may therefore serve as a promising therapeutic target.

Funder

National Natural Science Foundation of China

Project of the Scientific, Technologic Bureau of Wuxi

Youth Program of Shanghai Municipal Commission of Health and Family Planning

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,General Medicine

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