PLCD1-Induced DNA Damage Inhibits the Tumor Growth via Downregulating CDKs in Chondrosarcoma

J Oncol. 2022 Jul 4:2022:4488640. doi: 10.1155/2022/4488640. eCollection 2022.

Abstract

Purpose: Typical genes for the treatment and diagnosis of high-grade chondrosarcoma are still in need. Our study aimed to explore the PLCD1 function in chondrosarcoma for further treatment.

Materials and methods: Our study collected the information of 49 patients in our department. The PLCD1 expression in our cohort was detected and was compared with the TCGA database. PLCD1 knockdown and overexpression cell lines were established stably. Cell viability assay and colony formation assay were performed for cell proliferation. Flow cytometry analysis was performed for cell cycle and apoptosis. Western blotting was performed for PLCD1-related protein expression. Animal xenografts were established to verify the effect of PLCD1 in high-grade chondrosarcoma.

Results: Compared with the TCGA database, the relation between PLCD1 expression and the malignancy of chondrosarcoma was demonstrated. A lower PLCD1 expression was detected mainly in high-grade chondrosarcoma. PLCD1 overexpression in high-grade chondrosarcoma suppressed CDKs/cyclins and induced DNA damage causing cell cycle blocking and apoptosis. Antitumor effect of PLCD1 overexpression was verified in vivo.

Conclusion: Lower PLCD1 was expressed in high-grade chondrosarcoma. Overexpressed PLCD1-induced DNA damage caused cell cycle blocking and apoptosis in vitro and in vivo. PLCD1 could be a novel target in high-grade chondrosarcoma for further drug development.