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Published on: March 20, 2016
DLST mediates the malignant progression of osteosarcoma cells by regulating the p38 MAPK signaling pathway
Chong Guo1, Kaiqiong Liao2, Kai Xu1
1Department of Orthopedics, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330008, China; Jiangxi Key Laboratory of Oncology, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330008, China; Medical Department of Graduate School, Nanchang University, Nanchang, Jiangxi, 330006, China.
Background:
This research investigates the function of dihydrolipoic acid succinyltransferase (DLST) in the initiation and progression of osteosarcoma.
Methods:
Cellular functions were assessed using CCK-8, colony formation, scratch assays, transwell assays, and flow cytometry. The expression of relevant genes at both mRNA and protein levels was detected using quantitative real-time PCR (qRT-PCR) and Western blotting techniques. The regulatory mechanism of DLST was analyzed through RNA-sequencing. Finally, tumor growth in vivo was evaluated using established animal models.
Results:
DLST was highly expressed in osteosarcoma. Knockdown of DLST limited the proliferative, migratory, invasive, and anti-apoptotic abilities of osteosarcoma cells. RNA-seq was employed to analyze its mechanism, which showed that DLST can influence the p38 MAPK signaling pathway. Functional validation further showed that the p38 MAPK signaling pathway inhibitor was able to reverse the malignant functional changes in osteosarcoma cells that had been caused by DLST knockdown. Finally, in in vivo experiments, knocking down the DLST gene in the osteosarcoma animal model slowed down tumor growth.
Conclusion:
In this study, we found that DLST promotes the proliferation, migration, invasion, anti-apoptosis of osteosarcoma cells, as well as tumor growth, regulated through the p38 MAPK signaling pathway. These results could offer novel and valuable perspectives for the clinical management of osteosarcoma.
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