Related Experiment Video
Updated: Oct 19, 2025
A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
Non-small cell lung cancer cell-derived exosomal miR-17-5p promotes osteoclast differentiation by targeting PTEN
Mengyan Wang1, Mingna Zhao1, Qiaomei Guo1
1Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, China.
Abstract:
Aberrant activity of bone resorbing osteoclasts plays a key role in the development of osteoporosis and cancer bone metastasis. The identification of novel and specific targets will be helpful for the development of new therapeutic strategies for bone metastasis in lung cancer. Herein, we examined microRNAs in tumor cell-derived exosomes to investigate the communication between the bone environment and tumor cells. TCGA database analysis showed that the level of miR-17-5p increased in non-small cell lung cancer tissues compared with non-tumor tissues. To investigate the function of exosomes in inducing osteoclastogenesis, osteoclast precursors were incubated with exosomes isolated from non-small cell lung cancer cell line, as well as receptor activator of NF-KB ligand and M-CSF to induce osteoclastogenesis. We found that exosomal miR-17-5p is upregulated in a non-small cell lung cancer cell line with bone metastasis compared with the original cell line. Overexpression of miR-17-5p enhanced the osteoclastogenesis of RAW264.7 cells. PTEN was identified as a direct target of miR-17-5p and showed negative effects on osteoclastogenesis. Importantly, treatment of LY294002 (an inhibitor of the PI3K/Akt pathway) attenuated miR-17-5p-mediated osteoclastogenesis effects. Taken together, our findings demonstrated that miR-17-5p promotes osteoclastogenesis through the PI3K/Akt pathway via targeting PTEN in lung cancer.
Insights
MicroRNA-17-5p in lung cancer exosomes promotes bone metastasis by enhancing osteoclast formation. Targeting this pathway offers a potential therapeutic strategy for bone metastasis in lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Aberrant osteoclast activity is crucial in osteoporosis and cancer bone metastasis.
- Targeting specific molecules is vital for developing new lung cancer bone metastasis therapies.
Purpose of the Study:
- To investigate microRNAs in tumor cell-derived exosomes for understanding bone and tumor cell communication.
- To explore the role of miR-17-5p in lung cancer-associated osteoclastogenesis.
Main Methods:
- TCGA database analysis to assess miR-17-5p levels in non-small cell lung cancer (NSCLC).
- Isolation of exosomes from NSCLC cell lines and incubation with osteoclast precursors.
- Overexpression of miR-17-5p in RAW264.7 cells and PTEN interaction analysis.
- Assessment of the PI3K/Akt pathway using LY294002 inhibitor.
Main Results:
- miR-17-5p was upregulated in NSCLC tissues and exosomes from bone metastatic NSCLC cell lines.
- Exosomal miR-17-5p overexpression enhanced osteoclastogenesis in RAW264.7 cells.
- PTEN was identified as a direct target of miR-17-5p, inhibiting osteoclastogenesis.
- Inhibition of the PI3K/Akt pathway attenuated miR-17-5p-induced osteoclastogenesis.
Conclusions:
- miR-17-5p promotes osteoclastogenesis via the PI3K/Akt pathway by targeting PTEN in lung cancer.
- Exosomal miR-17-5p is a key mediator in the communication between lung cancer cells and the bone microenvironment.
- Targeting exosomal miR-17-5p presents a potential therapeutic avenue for lung cancer bone metastasis.
