Knockdown of GTF2E2 inhibits the growth and progression of lung adenocarcinoma via RPS4X in vitro and in vivo.

ABSTRACT:

Background

Lung adenocarcinoma (LUAD) is one of the most common malignancies worldwide. However, the molecular mechanism of LUAD tumorigenesis and development remains unclear. The purpose of this study was to comprehensively illustrate the role of GTF2E2 in the growth and progression of LUAD.

Methods and materials

We obtained the mRNA expression data from The Cancer Genome Atlas, Gene Expression Omnibus database, and our institution. Systematic bioinformatical analyses were performed to investigate the expression and prognostic value of GTF2E2 in LUAD. The results were validated by immunohistochemistry and qPCR. The effect of knocking down GTF2E2 using two short hairpin RNAs was investigated by in vitro and in vivo assays. Subsequently, shotgun liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analyses were applied to identified potential GTF2E2 interacting proteins, and the downstream molecular mechanisms of GTF2E2-signaling were further explored by a series of cellular functional assays.

Results

We found that GTF2E2 expression was significantly increased in LUAD tissue compared with adjacent normal tissue and was negatively associated with patients' overall survival. Besides, we demonstrated that GTF2E2 knockdown inhibited LUAD cell proliferation, migration, invasion, and promote apoptosis in vitro, as well as attenuated tumor growth in vivo. Results from LC-MS/MS suggested that RPS4X might physically interact with GTF2E2 and mediated GTF2E2's regulatory effect on LUAD development through the mTOR pathway.

Conclusion

Our findings indicate that GTF2E2 promotes LUAD development by activating RPS4X. Therefore, GTF2E2 might serve as a promising biomarker for the diagnosis and prognosis of LUAD patients, thus shedding light on the precise and personalized therapy for LUAD in the future.

SUBMITTER: Bi G 

PROVIDER: S-EPMC7989205 | biostudies-literature |

REPOSITORIES: biostudies-literature