MLN51 (Metastatic Lymph Node Gene 51)/CASC3 (Cancer Susceptibility Candidate Gene 3), A Putative Tumour Suppressor in Breast Cancer, the Clinical and Therapeutic Connections

Binbin Cong,1,2 Tracey A Martin,2 Xiaoshan Cao,1,2 Fiona S Ruge,2 Amber Xinyu Li,2 Robert E Mansel,3 Yongsheng Wang,1 Wen G Jiang2 1Breast Cancer Centre, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, Cardiff University School of Medicine, Cardiff, UK; 3Wales Breast Centre, University Llandough Hospital, Cardiff, UKCorrespondence: Wen G Jiang, Email [email protected]: The Metastatic Lymph Node Gene 51 Protein (MLN51), also known as the Cancer Susceptibility Candidate Gene 3 Protein, was first identified in malignant breast tumours. It has been shown to be a key component of the exon junction complex. This study aimed to evaluate the prognostic value of MLN51 expression in breast cancer.Methods: MLN51 expression was evaluated in a Cardiff clinical breast cancer cohort (n = 127) and in The Cancer Genome Atlas breast cancer database. The MLN51 protein was detected by immunohistochemistry. Two groups of breast cancer cell line models were created, namely MLN51 expression activation by transcriptional activation in MLN51 negative cells, and MLN51 knockdown by shRNA in MLN51 positive cells. Cell models were used to study the effect of the expression of the MLN51 gene in their behavior.Results: High expression of the MLN51 transcript was significantly correlated with favourable overall survival and disease free survival (p = 0.004 and p = 0.001, respectively). Patients who responded to chemotherapy had significantly higher MLN51 levels than those who resisted treatment (p = 0.00054), and this connection was more profound in ERBB2 negative type. Following activation of MLN51 in MDA MB-231cells, there was a significant decrease in the growth rate. In contrast, the knockdown of MLN51 in SKBR3 cells significantly increased cell growth. High expression of MLN51 following transcriptional activation increases the sensitivity to chemotherapy and anti-ERBB2 target therapy.Conclusion: MLN51 expression is an independent predictor of disease prognosis, patient survival, and treatment response in breast cancer patients.Keywords: breast cancer, MLN51, CASC3, disease prognosis, therapy response