Targeting diacylglycerol kinase α impairs lung tumorigenesis by inhibiting cyclin D3
Dong Zhou1,2, Tao Liu1,2, Xinrui Rao1,2
1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background:
Diacylglycerol kinase α (DGKA) is the first member discovered from the diacylglycerol kinase family, and it has been linked to the progression of various types of tumors. However, it is unclear whether DGKA is linked to the development of lung cancer.
Methods:
We investigated the levels of DGKA in the lung cancer tissues. Cell growth assay, colony formation assay and EdU assay were used to examine the effects of DGKA-targeted siRNAs/shRNAs/drugs on the proliferation of lung cancer cells in vitro. Xenograft mouse model was used to investigate the role of DGKA inhibitor ritanserin on the proliferation of lung cancer cells in vivo. The downstream target of DGKA in lung tumorigenesis was identified by RNA sequencing.
Results:
DGKA is upregulated in the lung cancer cells. Functional assays and xenograft mouse model indicated that the proliferation ability of lung cancer cells was impaired after inhibiting DGKA. And cyclin D3(CCND3) is the downstream target of DGKA promoting lung cancer.
Conclusions:
Our study demonstrated that DGKA promotes lung tumorigenesis by regulating the CCND3 expression and hence it can be considered as a potential molecular biomarker to evaluate the prognosis of lung cancer patients. What's more, we also demonstrated the efficacy of ritanserin as a promising new medication for treating lung cancer.
Insights
Diacylglycerol kinase α (DGKA) promotes lung cancer by upregulating cyclin D3 (CCND3). Inhibiting DGKA with ritanserin shows promise for lung cancer treatment and prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Diacylglycerol kinase α (DGKA) is implicated in various cancers.
- Its role in lung cancer development remains largely uninvestigated.
Purpose of the Study:
- To investigate the role of DGKA in lung cancer.
- To identify DGKA's downstream targets in lung tumorigenesis.
- To evaluate ritanserin as a potential lung cancer therapeutic.
Main Methods:
- DGKA expression analysis in lung cancer tissues.
- In vitro proliferation assays (cell growth, colony formation, EdU) using DGKA inhibitors.
- In vivo xenograft mouse model with ritanserin treatment.
- RNA sequencing to identify downstream targets.
Main Results:
- DGKA is significantly upregulated in lung cancer cells.
- Inhibition of DGKA suppressed lung cancer cell proliferation in vitro and in vivo.
- Cyclin D3 (CCND3) was identified as a key downstream target of DGKA in lung cancer.
Conclusions:
- DGKA promotes lung tumorigenesis via CCND3 regulation, serving as a potential prognostic biomarker.
- Ritanserin demonstrates efficacy as a therapeutic agent for lung cancer.
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