ARNTL2 is an indicator of poor prognosis, promotes epithelial-to-mesenchymal transition and inhibits ferroptosis in lung adenocarcinoma

Huan Zhang; Guangyao Shan; Xing Jin; Xiangyang Yu; GuoShu Bi; Mingxiang Feng; Hao Wang; Miao Lin; Cheng Zhan; Qun Wang; Ming Li

doi:10.1016/j.tranon.2022.101562

ARNTL2 is an indicator of poor prognosis, promotes epithelial-to-mesenchymal transition and inhibits ferroptosis in lung adenocarcinoma

Transl Oncol. 2022 Dec:26:101562. doi: 10.1016/j.tranon.2022.101562. Epub 2022 Oct 10.

Authors

Huan Zhang¹, Guangyao Shan¹, Xing Jin¹, Xiangyang Yu², GuoShu Bi¹, Mingxiang Feng¹, Hao Wang¹, Miao Lin¹, Cheng Zhan¹, Qun Wang¹, Ming Li³

Affiliations

¹ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Thoracic Surgery, Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital/Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China.
³ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: li_m14@fudan.edu.cn.

Abstract

Objectives: ARNTL2, as a circadian transcription factor, has been recently proposed to play an important role in a variety of tumors. however, the role of ARNTL2 in lung carcinogenesis and progression remains unclear. The purpose of this study was to investigate the effect of ARNTL2 on the clinical characteristics and prognosis of lung adenocarcinoma and to explore the relationship between ARNTL2 and EMT, ferroptosis in lung adenocarcinoma.

Methods: The Cancer Genome Atlas (TCGA) database's multi-omics data were downloaded using the Xena browser. Based on the expression levels of ARNTL2, patients with lung adenocarcinoma from TCGA were divided into two groups: those with high ARNTL2 expression and those with low ARNTL2 expression. ARNTL2 was studied for its effects on lung adenocarcinoma's clinicopathological, genomic, and immunological characteristics. Furthermore, in vivo and in vitro assays were used to confirm the impact of ARNLT2 knockdown on lung adenocarcinoma cells.

Results: We found ARNTL2 is highly expressed in lung adenocarcinoma and was an independent predictor of a poor prognosis in patients with lung adenocarcinoma. In addition, we demonstrated that knockdown of ARNTL2 promoted ferroptosis, inhibited EMT, cell proliferation, migration and invasion in lung adenocarcinoma. In contrast, overexpressing ARNTL2 yielded the opposite results.

Conclusions: ARNTL2 is an independent unfavorable prognostic factor for lung adenocarcinoma. It plays a facilitating role in the development of lung adenocarcinoma, especially in promoting EMT and inhibiting ferroptosis, revealing that ARNTL2 may be a potential biomarker for lung adenocarcinoma.

Keywords: ARNTL2; EMT; Ferroptosis; Lung adenocarcinoma.