Research Paper Advance Articles
MATN4 as a target gene of HIF-1α promotes the proliferation and metastasis of osteosarcoma
- 1 School of Clinical Medicine, Guizhou Medical University, Guiyang 550000, Guizhou, China
- 2 Department of Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou, China
- 3 Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou, China
- 4 Department of Bone and Joint Surgery, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang 550000, Guizhou, China
- 5 Department of Pathology, The Afflicted Hospital of Guizhou Medical University, Guiyang 550000, Guizhou, China
- 6 Transformation Engineering Research Center of Chronic Disease Diagnosis and Treatment, Guizhou Medical University, Guiyang 550000, China
- 7 Department of Orthopedics, Guiyang Maternal and Child Health-Care Hospital, Guiyang 550000, China
Received: August 28, 2023 Accepted: March 3, 2024 Published: June 17, 2024
https://doi.org/10.18632/aging.205941How to Cite
Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Osteosarcoma is a highly malignant bone tumor that exhibits rapid growth and early metastasis. Hypoxia plays a pivotal role in promoting the proliferation and metastasis of osteosarcoma through a series of molecular events, which are partially mediated and regulated by HIF-1α. However, the regulatory network associated with HIF-1α in osteosarcoma remains limited. Therefore, the objective of this study was to identify critical hypoxia-associated genes and investigate their effects and molecular mechanisms in osteosarcoma cells.
Methods: Through bioinformatics analysis, matrilin-4 (MATN4) was identified as a crucial gene associated with hypoxia. The expression of MATN4 and HIF-1α was assessed using immunohistochemistry, RT-qPCR, and western blotting. The proliferative capacity of osteosarcoma cells was assessed through the utilization of CCK-8, EDU staining, and colony formation assays. The effects of MATN4 on the mobility of OS cells were evaluated using wound-healing assays and transwell assays. The interaction between MATN4 and HIF-1α was detected through chromatin immunoprecipitation.
Results: MATN4 is overexpressed in osteosarcoma tissue and cells, particularly in osteosarcoma cells with high metastatic potential. Knockdown of MATN4 inhibits the proliferation, migration, and invasion abilities of osteosarcoma cells and reverses the promoting effects of hypoxia on these functions. Additionally, HIF-1α binds to MATN4 and upregulates its expression. Interestingly, knockdown of HIF-1α reduces the stimulatory effects of MATN4 overexpression on the proliferation, migration, and invasion of osteosarcoma cells under hypoxic conditions.
Conclusions: Taken together, our results suggest that MATN4 is regulated by HIF-1α and confers a more aggressive phenotype on OS cells. This evidence suggests that MATN4 may act as a potential target for OS diagnosis and treatment.