MiR-93 enhances angiogenesis and metastasis by targeting LATS2.

Abstract

Here we report that miR-93, a miRNA in the miR-106B~25 cluster, a paralog of the miR-17-92 cluster, was significantly upregulated in human breast carcinoma tissues. We stably expressed miR-93 in the MT-1 human breast carcinoma cell line and found that tumors formed by the miR-93 cells contained more blood vessels than those formed by the control cells. Co-culture experiments indicated that the MT-1 cells displayed a high activity of adhesion with endothelial cells and could form larger and more tube-like structures with endothelial cells. Lung metastasis assays were performed in a mouse metastatic model, and it was found that expression of miR-93 promoted tumor cell metastasis to lung tissue. In cell culture, expression of miR-93 enhanced cell survival and invasion. We examined the potential target that mediated miR-93's effects and found that the large tumor suppressor, homology 2 (LATS2) was a target of miR-93. Higher levels of LATS2 were associated with cell death in the tumor mass. Silencing LATS2 expression promoted cell survival, tube formation and invasion, while ectopic expression of LATS2 decreased cell survival and invasion. These findings demonstrated that miR-93 promoted tumor angiogenesis and metastasis by suppressing LATS2 expression. Our results suggest that the inhibition of miR-93 function may be a feasible approach to repress tumor metastasis.

• Authors: Ling Fang, William W Du, Weining Yang, Zina Jeyapalan Rutnam, Chun Peng, Haoran Li, Yunxia Q O'Malley, Ryan W Askeland, Sonia Sugg, Mingyao Liu, Tanvi Mehta, Zhaoqun Deng, Burton B Yang
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 11 Issue 23 Pg. 4352-65 (Dec 01 2012) ISSN: 1551-4005 [Electronic] United States
• PMID: 23111389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN93 microRNA, human
• MicroRNAs
• RNA, Small Interfering
• Tumor Suppressor Proteins
• LATS2 protein, human
• Protein Serine-Threonine Kinases

Topics

• Animals
• Base Sequence
• Breast Neoplasms (blood supply, metabolism, pathology)
• Cell Line
• Cell Movement
• Cell Survival
• Coculture Techniques
• Disease Models, Animal
• Endothelial Cells (cytology, metabolism)
• Female
• Humans
• Lung Neoplasms (pathology, secondary)
• Mice
• Mice, Nude
• Mice, SCID
• MicroRNAs (metabolism)
• Neovascularization, Pathologic
• Protein Serine-Threonine Kinases (antagonists & inhibitors, genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Transplantation, Heterologous
• Tumor Suppressor Proteins (antagonists & inhibitors, genetics, metabolism)