# LncRNA LOC610012 Inhibits Canine Mammary Tumor Activity via the PTGS2/EP3 and GSK3β Signaling Pathways

## TL;DR

A new long non-coding RNA, LOC610012, was found to suppress canine mammary tumor growth by affecting specific signaling pathways.

## Contribution

The study identifies LOC610012 as a novel tumor suppressor lncRNA in canine mammary tumors.

## Key findings

- LOC610012 is downregulated in canine mammary tumor tissues and cells.
- LOC610012 inhibits tumor cell proliferation, invasion, and metastasis in vitro and in vivo.
- LOC610012 causes mitochondrial damage and reduces cell viability through the PTGS2/EP3 and GSK3β pathways.

## Abstract

Canine mammary tumors (CMTs) are the common tumors in female dogs, and approximately 50% of CMTs are malignant tumors, with abnormal regulation of non-coding RNAs being a critical factor in disease progression. Currently, research on long non-coding RNAs (lncRNAs) regulating CMT development remains limited. This study identified a novel lncRNA, aiming to explore the role of lncRNA LOC610012 in CMTs. In this study, immunofluorescence and Western blot analyses were employed to detect protein expression. LncRNA LOC610012 is downregulated in CMT tissues and cells. Stable cells of LOC610012 were constructed by the lentivirus technique. Through a variety of experimental methods, LOC610012 inhibited the proliferation, invasion, and metastasis of CMT cells in in vitro and in vivo experiments conducted using cell culture and mouse models. Mechanistically, LOC610012 regulated the expression of EP3 and GSK-3β by targeting PTGS2, resulting in excessive production of reactive oxygen species (ROS), which inhibited cell viability. Similarly, through transmission electron microscopy, mitochondrial damage caused by LOC610012 was observed in CMT cells, which was manifested as mitochondrial swelling, membrane rupture, and mitochondrial ridge disappearance. PTGS2 could partially restore the inhibition of LOC610012 on cell activity. LOC610012 acts as a tumor suppressor gene in CMTs and as a potential biomarker for the disease.