MLN51 (Metastatic Lymph Node Gene 51)/CASC3 (Cancer Susceptibility Candidate Gene 3), A Putative Tumour Suppressor in
Binbin Cong1,2, Tracey A Martin2, Xiaoshan Cao1,2
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.
Introduction:
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.
Insights
Metastatic Lymph Node Gene 51 Protein (MLN51) expression predicts better breast cancer survival and treatment response. High MLN51 levels correlate with improved prognosis and chemotherapy sensitivity, especially in ERBB2-negative types.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastatic Lymph Node Gene 51 Protein (MLN51), also known as Cancer Susceptibility Candidate Gene 3 Protein, is implicated in breast cancer.
- MLN51 is a key component of the exon junction complex, suggesting a role in RNA processing and gene expression regulation.
Purpose of the Study:
- To investigate the prognostic value of MLN51 expression in breast cancer.
- To determine the correlation between MLN51 levels and patient survival, disease-free survival, and response to chemotherapy.
Main Methods:
- MLN51 expression was assessed using immunohistochemistry in a clinical breast cancer cohort (n=127) and The Cancer Genome Atlas database.
- Cell line models were created to study MLN51 activation and knockdown effects on cell behavior and treatment sensitivity.
Main Results:
- High MLN51 transcript expression significantly correlated with favorable overall survival (p=0.004) and disease-free survival (p=0.001).
- Patients responding to chemotherapy exhibited significantly higher MLN51 levels (p=0.00054), particularly in ERBB2-negative breast cancer.
- MLN51 activation decreased cell growth and increased sensitivity to chemotherapy and anti-ERBB2 therapy, while knockdown increased cell growth.
Conclusions:
- MLN51 expression serves as an independent predictor of breast cancer prognosis.
- MLN51 levels are associated with patient survival and response to therapeutic interventions.
- MLN51 modulation impacts breast cancer cell growth and treatment sensitivity, highlighting its therapeutic potential.
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