MRN (MRE11-RAD50-NBS1) Complex in Human Cancer and Prognostic Implications in Colorectal Cancer.

Yiling Situ,Vincent Ho,Liping Chung,Cheok Lee

doi:10.3390/ijms20040816

Abstract

The MRE11-RAD50-NBS1 (MRN) complex has been studied in multiple cancers. The identification of MRN complex mutations in mismatch repair (MMR)-defective cancers has sparked interest in its role in colorectal cancer (CRC). To date, there is evidence indicating a relationship of MRN expression with reduced progression-free survival, although the significance of the MRN complex in the clinical setting remains controversial. In this review, we present an overview of the function of the MRN complex, its role in cancer progression, and current evidence in colorectal cancer. The evidence indicates that the MRN complex has potential utilisation as a biomarker and as a putative treatment target to improve outcomes of colorectal cancer.

Highlights

Colorectal cancer (CRC) is the second most commonly diagnosed malignancy in females, the third most commonly diagnosed malignancy in males, and has the third highest global mortality rate [1,2]
Surgical resection combined with chemotherapy is the standard treatment for colon cancer, whereas surgical resection combined with neoadjuvant radiotherapy is preferred for rectal cancer [7,8]
Low MRN expression occurred more commonly in the neoadjuvant radiotherapy group High meiotic recombination 11 (MRE11) expression was associated with worse OS in the low-grade tumours

Summary

Introduction

Colorectal cancer (CRC) is the second most commonly diagnosed malignancy in females, the third most commonly diagnosed malignancy in males, and has the third highest global mortality rate [1,2]. The MRE11-RAD50-NBS1 (MRN) complex plays an important role in DNA damage response (DDR) and the repair pathway of double-strand breaks (DSBs). The MRN complex is heterotrimer consisting of meiotic recombination 11 (MRE11), DNA repair protein Rad (RAD50), and Nijmegen breakage syndrome 1 (NBS1) (Figure 1A) It is the major catalytic protein complex in coordinating and sensing DSBs and in initiating the DNA damage response pathway. Once the DDR pathway is activated, it results in activation of ataxia telangiectasia mutated (ATM) dimers, repairing DSBs through complex machinery at different stages including cell cycle checkpoints, telomere length maintenance, and meiosis [15,16,17] This is done via extensive protein-protein interactions, ATP hydrolysis, endonuclease and exonuclease activities, and coordinating re-joining of repaired DNA strands [18].

The Role of the MRN Complex in Colorectal Cancer

Results

MRN Protein Complex and Sensitivity to Chemoradiation in Colorectal Cancer

Conclusions