COL5A1 may contribute the metastasis of lung adenocarcinoma.

Abstract

BACKGROUND:

Lung cancer leads to the largest number of cancer-related deaths worldwide and is usually accompanied with metastasis which is the primary cause of those death and correlated with poor prognosis. However, the mechanism of lung cancer metastasis is still lack of definition.

METHODS:

We compared the primary lung adenocarcinoma (AD) and its metastasis tissues induced by overexpression of KrasG12D and inactivation of P53 in mouse lungs by analyzing GSE40222 about the differentially expressed genes (DEGs), pathways and hub genes. And human lung AD databases are used to verify the conversed changes of identified key gene and then followed functional studies are performed to explore the functions of key gene.

RESULTS:

We identified 165 genes differentially expressed in lung AD metastasis compared to primary AD. Pathway analysis identified 649 GO biological processes and 8 KEGG pathways, such as ECM-receptor interaction. Biological network interaction identified the hub genes during lung adenocarcinoma metastasis, such as the up-regulated COL5A1, a novel gene in AD metastasis. We found it's also increased in human AD and advanced stage. Knockdown of COL5A1 in human AD metastatic cells inhibited cell growth and invasion, and induced cell apoptosis. Notably, higher expression of COL5A1 was observed in the lung AD patients with recurrence and short survive.

CONCLUSION:

By analyzing mouse lung AD and its metastases, we identified the potential key genes and pathways regulating lung AD metastasis, such as COL5A1. The following analysis of COL5A1 in human AD database and cells explores its functions, holding the implications of target therapy in AD metastasis and also providing more clues for future studies.

• Authors: Weibo Liu, Haifeng Wei, Zhengyu Gao, Guanghui Chen, Yujie Liu, Xin Gao, Guangjian Bai, Shaohui He, Tielong Liu, Wei Xu, Xinghai Yang, Jian Jiao, Jianru Xiao
• Journal: Gene (Gene) Vol. 665 Pg. 57-66 (Jul 30 2018) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 29702185 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• COL5A1 protein, human
• Collagen Type V
• Tumor Suppressor Protein p53
• Hras protein, mouse
• Proto-Oncogene Proteins p21(ras)

Topics

• Adenocarcinoma (genetics, metabolism, pathology)
• Adenocarcinoma of Lung
• Amino Acid Substitution
• Animals
• Collagen Type V (biosynthesis, genetics)
• Databases, Nucleic Acid
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Mice
• Mutation, Missense
• Neoplasm Metastasis
• Proto-Oncogene Proteins p21(ras) (genetics, metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)