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ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma.

ABSTRACT: Lung adenocarcinoma (LUAD) is a lethal malignancy with metastasis, a major tumor feature that predominantly correlated with progression, but the molecules that mediated tumor metastasis remain elusive. To declare the critical regulatory genes, RNA sequencing data in LUAD patients was acquired from The Cancer Genome Atlas (TCGA) and found that ALDH3A1 was distinctly highly expressed in LUAD patients with metastasis (M1) compared with those without metastasis (M0), linked to the property of cancer stem cell and epithelial-mesenchymal transition (EMT). Besides, high ALDH3A1 expression predicted a poor prognosis. Knockdown of ALDH3A1 showed decreased proliferation, migration, and invasion in A549 cell line. Furthermore, BAG1 was regulated by ALDH3A1 through p53, enhanced cell proliferation, and predicted clinical prognosis. Our findings collectively uncovered a novel mechanism that orchestrates tumor cells' metastasis, and decreasing ALDH3A1 represented a potential therapeutic target for reprogramming metastasis.

SUBMITTER: Fan F

PROVIDER: S-EPMC8247369 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLocal relapses and metastases are primary causes of death in lung cancer patients. In the present study, we aimed to develop a prognostic signature based on metastasis-associated lncRNAs in patients with lung adenocarcinoma (LUAD).MethodsFirstly, the potential metastasis-associated lncRNAs were identified by analyzing high-throughput data from The Cancer Genome Atlas (TCGA), and based on which, an lncRNA signature was constructed for prediction of relapse in LUAD patients using Cox proportional hazards regression analysis. Moreover, the prognostic performance of the lncRNA signature was evaluated using Kaplan-Meier survival analysis, time-dependent receiver operating characteristic (ROC) curve and Cox analysis, respectively. In addition, the potential metastasis-associated function of these six lncRNAs was confirmed by lncRNA over-expression or depletion and in vitro transwell assays in LUAD cells.ResultsAn lncRNA signature consisting of six most important prognostic factors (LINC01819, ZNF649-AS1, HNF4A-AS1, FAM222A-AS1, LINC02323 and LINC00672) was developed. The signature was an independent predictor for patients' relapse-free survival (RFS), which could provide higher tumor relapse prediction capability compared with the TNM staging system at three years and five years, respectively (P = 0.0209 and P = 0.0468). Furthermore, the combination of this lncRNA signature and TNM stage had better prognostic value than TNM stage alone at three and five years, respectively (P = 0.0006 and P = 0.0096). Additionally, all the lncRNAs of the signature had a regulatory role in the LUAD cell mobility.ConclusionsThis novel six-lncRNA signature had considerable prognostic value for prediction of relapse in LUAD patients.Key pointsSignificant findings of the study The unique metastasis-associated lncRNA signature was related to tumor metastasis and prognosis in LUAD patients. What this study adds This signature had considerable prognostic value for prediction of relapse in LUAD patients.

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ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma.

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