LINC01585 functions as a regulator of gene expression by the CAMP/CREB signaling pathway in breast cancer.

Abstract

OBJECTIVE:

Breast cancer is the leading cause of cancer death among women. Nowadays, long non-coding RNAs (lncRNAs) have been identified and emerged as critical bio-markers in breast cancer tumorigenesis and progression. However, only a handful of lncRNAs which are implicated in BC have been characterized. The underlying molecular mechanisms are still largely unknown.

METHODS:

In this study, we explored 12 nominated lncRNAs at breast cancer susceptibility loci identified by genome-wide association studies to contribute to the risk and effects of breast cancer. We then analyzed these lncRNAs in a total of 132 pairs of breast cancer tissues and surrounding non-tumor tissues from southern China population.

RESULTS:

Here, we report a novel lncRNA, LINC01585, is aberrantly down regulated during breast cancer (BC). Next, to explore the molecular mechanisms underlying the biological activity of LINC01585, we identified LINC01585 binding protein by RNA pull-down experiments. Functionally, we found that LINC01585 overexpression inhibited breast cancer proliferation and growth by prototypical experiments. Mechanistically, LINC01585 was located in nuclear and binding with NONO protein. Interestingly, when LINC01585 was down-expressed, NONO separated from LINC01585 and then interacted with CRTC. The complex promotes CAMP/CREB target gene transcription and thus promotes the growth of breast cancer.

CONCLUSIONS:

A series of discoveries suggest to us that LINC01585 has a potential value in anti-carcinoma therapy and deserves further investigation.

• Authors: Rui Ma, Xiaoming Zhai, Xun Zhu, Liyuan Zhang
• Journal: Gene (Gene) Vol. 684 Pg. 139-148 (Feb 05 2019) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 30366079 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Cyclic AMP Response Element-Binding Protein
• RNA, Long Noncoding
• Cyclic AMP

Topics

• Breast Neoplasms (genetics)
• Cell Line, Tumor
• Cell Proliferation
• China
• Cyclic AMP (genetics, metabolism)
• Cyclic AMP Response Element-Binding Protein (genetics, metabolism)
• Female
• Gene Expression
• Gene Expression Regulation, Neoplastic (genetics)
• Genome-Wide Association Study
• Humans
• RNA, Long Noncoding (genetics, metabolism)
• Signal Transduction (genetics)