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

Bioengineered

Peng Wang¹  Yu Huang¹  Xin Xia¹  Lu Zhang¹  Wenzhi Zhao¹  Jian Han² 

[1] The Second Affiliated Hospital, Dalian Medical University;The Third People’s Hospital of Dalian, Non-directly Affiliated Hospital of Dalian Medical University;

关键词: phlda3;    mir-19a-3p;    akt/gsk3β;    osteosarcoma;    bioinformatics analysis;   

DOI  :  10.1080/21655979.2022.2031404

来源: DOAJ

【 摘 要 】

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/GSK3β 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/GSK3β axis has a pivotal role in osteosarcoma, and PHLDA3 is a prospective therapeutic target for treating osteosarcoma.

【 授权许可】

Unknown