Pleckstrin homology-like domain family A, member 3, a miR-19a-3p-regulated gene, suppresses tumor growth in osteosarcoma by downregulating the Akt pathway

Pleckstrin homology-like domain family A, member 3 (PHLDA3), is emerging as a critical regulator for multiple cancers. Nevertheless, the expression and role of PHLDA3 in osteosarcoma remain unknown. Herein, we purposed to elucidate the role of PHLDA3 in the progression and chemoresistance of osteosarcoma. According to the bioinformatics analysis, PHLDA3 expression was low in osteosarcoma patients, and low content was linked to poor prognosis. Additionally, activation of PHLDA3 suppressed osteosarcoma cell proliferation, migration, and chemoresistance, whereas PHLDA3 inhibition caused the opposite effects. Mechanistically, our data revealed that PHLDA3 negatively regulates the Akt/GSK3 beta signaling cascade in osteosarcoma. Furthermore, we found that miR-19a-3p might exert its oncogenic function by inhibiting PHLDA3 expression in osteosarcoma. These results demonstrated miR-19a-3p/PHLDA3/ Akt/GSK3 beta axis has a pivotal role in osteosarcoma, and PHLDA3 is a prospective therapeutic target for treating osteosarcoma.

Automated summary

The low expression of PHLDA3 is associated with poor prognosis in osteosarcoma patients. Activating PHLDA3 can suppress osteosarcoma cell proliferation, migration, and chemoresistance, while inhibiting PHLDA3 has the opposite effects. Furthermore, miR-19a-3p may exert its oncogenic function in osteosarcoma by inhibiting PHLDA3 expression.