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PLCD1诱导的DNA损伤通过下调软骨肉瘤中的细胞周期蛋白依赖性激酶抑制肿瘤生长。

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

作者信息

Shen Jiakang, Yu Chen, Wang Zhuoying, Mu Haoran, Cai Zhengdong

机构信息

Shanghai General Hospital of Nanjing Medical University, Shanghai, China.

Department of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

出版信息

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

DOI:10.1155/2022/4488640
PMID:35836489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9273466/
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.

摘要

目的

治疗和诊断高级别软骨肉瘤的典型基因仍有待发现。我们的研究旨在探索PLCD1在软骨肉瘤中的功能，以促进进一步治疗。

材料与方法

我们的研究收集了本部门49例患者的信息。检测了我们队列中PLCD1的表达，并与TCGA数据库进行了比较。稳定建立了PLCD1基因敲低和过表达的细胞系。进行细胞活力测定和集落形成测定以检测细胞增殖。进行流式细胞术分析以检测细胞周期和凋亡。进行蛋白质印迹法检测PLCD1相关蛋白的表达。建立动物异种移植模型以验证PLCD1在高级别软骨肉瘤中的作用。

结果

与TCGA数据库相比，证实了PLCD1表达与软骨肉瘤恶性程度之间的关系。主要在高级别软骨肉瘤中检测到较低的PLCD1表达。高级别软骨肉瘤中PLCD1过表达抑制了CDK/细胞周期蛋白，并诱导DNA损伤，导致细胞周期阻滞和凋亡。在体内验证了PLCD1过表达的抗肿瘤作用。

结论

高级别软骨肉瘤中PLCD1表达较低。过表达的PLCD1诱导的DNA损伤在体外和体内均导致细胞周期阻滞和凋亡。PLCD1可能成为高级别软骨肉瘤进一步药物研发的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/03002a28e79d/JO2022-4488640.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/44338a8be233/JO2022-4488640.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/9396dd14f6b0/JO2022-4488640.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/2509955ee9b6/JO2022-4488640.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/113996265b51/JO2022-4488640.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/03002a28e79d/JO2022-4488640.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/44338a8be233/JO2022-4488640.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/9396dd14f6b0/JO2022-4488640.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/2509955ee9b6/JO2022-4488640.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/113996265b51/JO2022-4488640.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/9273466/03002a28e79d/JO2022-4488640.005.jpg

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