# RNF135 Promotes Human Osteosarcoma Cell Growth and Inhibits Apoptosis by Upregulating the PI3K/AKT Pathway

## TL;DR

This study shows that RNF135 promotes osteosarcoma growth and prevents cell death by activating the PI3K/AKT pathway, suggesting it could be a new treatment target.

## Contribution

The study is the first to show RNF135's role in osteosarcoma via the PI3K/AKT pathway.

## Key findings

- RNF135 levels were significantly higher in osteosarcoma tissues compared to osteochondroma tissues.
- Knocking down RNF135 inhibited osteosarcoma cell growth and induced apoptosis.
- RNF135 knockdown reduced PI3K and p-AKT levels and activated caspase 3/7.

## Abstract

Ring finger protein 135 (RNF135) is an E3 ubiquitin ligase that has been implicated in the tumorigenesis of multiple human malignancies. However, whether RNF135 plays a role in the development of human osteosarcoma (OS) remains unknown.

RNF135 expression in 20 human OS and 20 human osteochondroma specimens were evaluated by means of immunohistochemistry staining. The effects of shRNA‐mediated RNF135 knockdown on human OS cell growth and apoptosis were evaluated through a panel of in vitro studies on cell proliferation, colony formation, exposure of phosphatidylserine on the cell surface, and caspase 3/7 activation. The protein levels of PI3K, AKT, and p‐AKT were determined by western blot analysis.

We detected significantly higher RNF135 levels in human OS tissues than human osteochondroma tissues. In in vitro studies, shRNA‐mediated RNF135 knockdown in human OS cells inhibited proliferation and induced apoptosis. In addition, RNF135 knockdown reduced PI3K and p‐AKT protein levels and activated caspase 3 and 7.

These results supported that RNF135 contributes to human OS development through PI3K/AKT‐dependent mechanisms. Targeting RNF135 may provide a new therapeutic approach for treating this human malignancy.