Int J Biol Sci 2021; 17(10):2622-2632. doi:10.7150/ijbs.59939 This issue

Research Paper

RHOV promotes lung adenocarcinoma cell growth and metastasis through JNK/c-Jun pathway

Deyu Zhang1#, Qiwei Jiang1#, Xiangwei Ge2, Yanzhu Shi3, Tianxing Ye4, Yue Mi1, Tian Xie1, Qihong Li5✉, Qinong Ye1✉

1. Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, P.R. China.
2. Department of Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China.
3. Medical College, Guizhou University, Guiyang 550025, P.R. China.
4. College of Medicine, Yanbian University, Yanji 133000, P.R. China.
5. Department of Stomatology, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100071, P.R. China.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Zhang D, Jiang Q, Ge X, Shi Y, Ye T, Mi Y, Xie T, Li Q, Ye Q. RHOV promotes lung adenocarcinoma cell growth and metastasis through JNK/c-Jun pathway. Int J Biol Sci 2021; 17(10):2622-2632. doi:10.7150/ijbs.59939. Available from https://www.ijbs.com/v17p2622.htm

File import instruction

Abstract

Graphic abstract

Lung adenocarcinoma (LUAD) is a common type of lung cancer with high frequent metastasis and a high death rate. However, genes responsible for LUAD metastasis are still largely unknown. Here, we identify an important role of ras homolog family member V (RHOV) in LUAD metastasis using a combination of bioinformatic analysis and functional experiments. Bioinformatic analysis shows five hub LUAD metastasis driver genes (RHOV, ZIC5, CYP4B1, GPR18 and TCP10L2), among which RHOV is the most significant gene associated with LUAD metastasis. High RHOV expression predicted shorter overall survival in LUAD patients. RHOV overexpression promotes proliferation, migration, and invasion of LUAD cells, whereas RHOV knockdown inhibits these biological behaviors. Moreover, knockdown of RHOV suppresses LUAD tumor growth and metastasis in nude mice. Mechanistically, RHOV activates Jun N-terminal Kinase (JNK)/c-Jun signalling pathway, an important pathway in lung cancer development and progression, and regulates the expression of markers of epithelial-to-mesenchymal transition, a process involved in cancer cell migration, invasion and metastasis. RHOV-induced malignant biological behaviors are inhibited by pyrazolanthrone, a JNK inhibitor. Our findings indicate a critical role of RHOV in LUAD metastasis and may provide a biomarker for prognostic prediction and a target for LUAD therapy.

Keywords: Lung adenocarcinoma, metastasis, JNK/c-Jun pathway, RHOV, bioinformatics