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

Feifei Fan; Ruxue Yin; Liuya Wang; Shunxin Zhao; Dan Lv; Kangli Yang; Shen Geng; Ningning Yang; Xiaohong Zhang; Hongmin Wang

doi:10.7150/jca.58250

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

J Cancer. 2021 Jun 11;12(16):4780-4790. doi: 10.7150/jca.58250. eCollection 2021.

Authors

Feifei Fan¹, Ruxue Yin², Liuya Wang³, Shunxin Zhao¹, Dan Lv¹, Kangli Yang¹, Shen Geng¹, Ningning Yang¹, Xiaohong Zhang⁴, Hongmin Wang¹

Affiliations

¹ Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
² Department of rheumatism and immunology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
³ The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
⁴ Department of Respiratory Medicine, Zhengzhou Central Hospital, Zhengzhou 450052, China.

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.

Keywords: ALDH3A1; lung adenocarcinoma; metastasis; prognosis; proliferation.