RESUMO
The epigenetic mechanism of tissue inhibitor of metalloproteinase 3 (TIMP3), a well-known tumor suppressor, in cervical cancer (CC) is still unclear. Integrated GEO database, protein interaction network, and a pan-cancer analysis revealed a KMT1A/TIMP3 axis in CC. KMT1A was highly expressed, and TIMP3 was poorly expressed in CC tissues and cells. KMT1A inhibited the activity of TIMP3. Silencing of KMT1A hampered the proliferation, migration, invasion, tumorigenesis and metastases of CC cells in vivo, and increased the apoptosis of cells. TIMP3 downregulation promoted the malignant phenotype and in vivo tumorigenesis and metastasis of CC cells. KMT1A downregulation impaired PI3K/AKT pathway in cells, while TIMP3 silencing promoted PI3K/AKT pathway activity. We propose a novel perspective that KMT1A involves in the growth and metastases via the TIMP3/PI3K/AKT axis in CC. In summary, our study identified a vital role played by KMT1A in the development of CC and the epigenetic mechanism, indicating that targeting KMT1A-related pathways could be conducive to the therapies for CC.
