RDM1 plays an oncogenic role in human lung adenocarcinoma cells

Lu Tong,Lei Li,Kun Li,Jian Liu,Wangjun Yan,Guoping Niu,Shihui Shen,Wenjiao Cao

doi:10.1038/s41598-018-30071-y

Abstract

RAD52 motif containing 1 (RDM1) is involved in DNA damage repair pathway and RDM1−/− cells increase sensitivity to cisplatin, a common chemotherapy drug. Lung cancer is the leading cause of cancer death worldwide. However, the role of RDM1 in lung cancer is unknown. Here, we find that the mRNA and protein expression levels of RDM1 are significantly increased in human lung tumors, especially in lung adenocarcinoma. The lung adenocarcinoma patients with higher mRNA expression of RDM1 show the worse clinical outcomes. Knockdown of RDM1 in lung adenocarcinoma cells reduces cell proliferation and promotes apoptosis, consistent with the role RDM1 in the overexpression experiments. Xenograft mouse model shows stable knockdown of RDM1 significantly inhibits lung adenocarcinoma tumor growth. These in vitro and in vivo results conclude that RDM1 plays an oncogenic role in human lung adenocarcinoma. Interestingly, P53/RAD51/RAD52 can be regulated by RDM1, and the negative regulation of P53 by RDM1 may be one of major mechanisms for RDM1 to accomplish its oncogenic functions in lung adenocarcinoma. Therefore, RDM1 may be a new target for the treatment of lung adenocarcinoma.

Highlights

The risk of cancer can be significantly increased by disruption of genomic integrity resulted from dysfunctional DNA damage response signaling and/or aberrant activity of the key components in the DNA repair pathways
We found that RAD52 motif containing 1 (RDM1) played an oncogenic role in human lung adenocarcinoma cells
Analyses of human lung cancer samples had shown that RDM1 was over-expressed in lung adenocarcinoma tumors, initializing the hypothesis that RDM1 may impose an oncogenic function in lung cancer

Summary

Introduction

The risk of cancer can be significantly increased by disruption of genomic integrity resulted from dysfunctional DNA damage response signaling and/or aberrant activity of the key components in the DNA repair pathways. We found that the mRNA and protein expressions of RDM1 were up-regulated in human lung adenocarcinoma samples. Results RDM1 is up-regulated in human lung adenocarcinoma tumors and correlated with poor clinical outcomes. Consistent with the Oncomine results, our immunohistochemistry (IHC) and Western Blot analyses showed the protein level of RDM1 in human lung adenocarcinoma in increased compared to that of adjacent normal lungs (Fig. 1B–D).

Results

Conclusion