biostudies-literatureChen LTalent Introduction and Research Start-up Foundation of the Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan People’s HospitalNatural Science Foundation of Guangdong ProvinceNatural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)786https://www.ebi.ac.uk/biostudies/studies/S-EPMC11530700biostudies-literatureUnknown15(11)OMA1 is an ATP-independent zinc metalloprotease essential for maintaining mitochondrial homeostasis and plays a vital role in tumorigenesis. Depending on the type of cancer, a decrease in OMA1 expression has been linked to a varying prognosis for patients. The role of OMA1 in human osteosarcoma (OS), one of the most prevalent malignant bone tumors, remains elusive. Here, we observed elevated OMA1 expression in OS tumor tissues from four patients with advanced OS. Knockout of OMA1 in OS cells significantly reduces OS tumor weight and size, and lung metastatic nodules in BALB/c nude mice. Immunohistochemistry analysis showed a significant decrease in Ki67 and an increase in Cleaved-caspase 3 in OMA1 knockout tumor samples. Mechanistically, we found that OMA1 deficiency increases the levels oCell death & diseaseInhibition of mitochondrial OMA1 ameliorates osteosarcoma tumorigenesis.PMC115307002023A15150102952022A1515012449Zhang DWXia XDPan YChen LLai BChen HChen DMo YfalseInhibition of mitochondrial OMA1 ameliorates osteosarcoma tumorigenesis.OMA1 is an ATP-independent zinc metalloprotease essential for maintaining mitochondrial homeostasis and plays a vital role in tumorigenesis. Depending on the type of cancer, a decrease in OMA1 expression has been linked to a varying prognosis for patients. The role of OMA1 in human osteosarcoma (OS), one of the most prevalent malignant bone tumors, remains elusive. Here, we observed elevated OMA1 expression in OS tumor tissues from four patients with advanced OS. Knockout of OMA1 in OS cells significantly reduces OS tumor weight and size, and lung metastatic nodules in BALB/c nude mice. Immunohistochemistry analysis showed a significant decrease in Ki67 and an increase in Cleaved-caspase 3 in OMA1 knockout tumor samples. Mechanistically, we found that OMA1 deficiency increases the levels o2024-01-01T00:00:00Z2024 Nov2026-07-15T05:19:34.908Z2025-04-21T21:51:00.791ZS-EPMC115307003948711810.1038/s41419-024-07127-1