LINC01355 suppresses breast cancer growth through FOXO3-mediated transcriptional repression of CCND1.

Abstract

Previously, several protein-coding tumor suppressors localized at 1p36 have been reported. In the present work, we focus on functional long non-coding RNAs (lncRNAs) embedded in this locus. Small interfering RNA was used to identify lncRNA candidates with growth-suppressive activities in breast cancer. The mechanism involved was also explored. LINC01355 were downregulated in breast cancer cells relative to non-malignant breast epithelial cells. Overexpression of LINC01355 significantly inhibited proliferation, colony formation, and tumorigenesis of breast cancer cells. LINC01355 arrested breast cancer cells at the G0/G1 phase by repressing CCND1. Moreover, LINC01355 interacted with and stabilized FOXO3 protein, leading to transcriptional repression of CCND1. Importantly, LINC01355-mediated suppression of breast cancer growth was reversed by knockdown of FOXO3 or overexpression of CCND1. Clinically, LINC01355 was downregulated in breast cancer specimens and correlated with more aggressive features. There was a negative correlation between LINC01355 and CCND1 expression in breast cancer samples. LINC01355 acts as a tumor suppressor in breast cancer, which is ascribed to enhancement of FOXO3-mediated transcriptional repression of CCND1. Re-expression of LINC01355 may provide a potential therapeutic strategy to block breast cancer growth and progression.

• Authors: Bolun Ai, Xiangyi Kong, Xiangyu Wang, Kai Zhang, Xue Yang, Jie Zhai, Ran Gao, Yihang Qi, Jing Wang, Zhongzhao Wang, Yi Fang
• Journal: Cell death & disease (Cell Death Dis) Vol. 10 Issue 7 Pg. 502 (06 26 2019) ISSN: 2041-4889 [Electronic] England
• PMID: 31243265 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Forkhead Box Protein O3
• RNA, Long Noncoding
• Cyclin D1

Topics

• Animals
• Blotting, Western
• Breast Neoplasms (genetics, metabolism, therapy)
• Cell Proliferation (genetics, physiology)
• Chromatin Immunoprecipitation
• Cyclin D1 (genetics, metabolism)
• Female
• Flow Cytometry
• Forkhead Box Protein O3 (genetics, metabolism)
• G1 Phase (genetics, physiology)
• Gene Expression Regulation, Neoplastic (genetics, physiology)
• Humans
• In Vitro Techniques
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Plasmids (genetics)
• RNA, Long Noncoding (genetics, physiology)
• Real-Time Polymerase Chain Reaction
• Resting Phase, Cell Cycle (genetics, physiology)
• Xenograft Model Antitumor Assays