Long noncoding RNA Linc00339 promotes triple-negative breast cancer progression through miR-377-3p/HOXC6 signaling pathway.

Abstract

Recently, long noncoding RNAs (lncRNAs) have become the key gene regulators and prognostic biomarkers in various cancers. Through microarray data, Linc00339 was identified as a candidate oncogenic lncRNA. We compared the expression levels of Linc00339 in several breast cancer cell lines and normal mammary gland epithelial cell line. The effects of Linc00339 on tumor progression were examined both in vitro and in vivo. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were applied to evaluate the functions of Linc00339, miR-377-3p, and HOXC6 on cell proliferation. Flow cytometry analysis was used to detect apoptosis and cell cycle distribution. Overall survival (OS) was analyzed using data from The Cancer Genome Atlas and molecular taxonomy of breast cancer international consortium (METABRIC). Dual luciferase assay and RNA immunoprecipitation were performed to confirm the interaction between Linc003339 and miR-377-3p. Linc00339 was increased in breast cancer cell lines compared with the normal epithelial cell. Through in vitro and in vivo experiments, Linc00339 overexpression promoted triple-negative breast cancer (TNBC) proliferation, inhibited cell cycle arrest, and suppressed apoptosis. Silencing of Linc00339 obtained the opposite effects. Mechanistic investigations demonstrated that Linc00339 could sponge miR-377-3p and regulate its expression. Higher expression of miR-377-3p indicated longer OS in breast cancer patients, especially in TNBC patients. Overexpression of miR-377-3p retarded TNBC cell growth through regulating cell cycle distribution and apoptosis. And miR-377-3p was involved in Linc00339-mediated TNBC proliferation through regulating HOXC6 expression. Knockdown of HOXC6 inhibited TNBC progression. In conclusion, our results illuminated that the novel Linc00339/miR-377-3p/HOXC6 axis played a critical role in TNBC progression and might be a promising therapeutic target for TNBC treatment.

• Authors: Xiaolong Wang, Tong Chen, Yan Zhang, Ning Zhang, Chen Li, Yaming Li, Ying Liu, Hanwen Zhang, Wenjing Zhao, Bing Chen, Lijuan Wang, Qifeng Yang
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 8 Pg. 13303-13317 (08 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30618083 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• HOXC6 protein, human
• Homeodomain Proteins
• MIRN377 microRNA, human
• MicroRNAs

Topics

• Animals
• Cell Cycle Checkpoints
• Cell Line, Tumor
• Cell Proliferation
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic (physiology)
• HEK293 Cells
• Homeodomain Proteins (metabolism)
• Humans
• Mice
• Mice, Nude
• MicroRNAs (metabolism)
• Neoplasms, Experimental
• RNA Interference
• Signal Transduction (physiology)
• Triple Negative Breast Neoplasms (metabolism)