ABSTRACT
Objective:To analyze the clinical data and related literature of sporadic amyotrophic lateral sclerosis (sALS) caused by a new mutation of MATR3 gene.Methods:A sALS patient with MATR3 gene mutation who was admitted to the Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital was collected. The examination of biochemistry, electromyography, cranial magnetic resonance imaging (MRI) and genetic tests, etc, were performed. Whole exon sequencing was performed to screen the disease-causing genes. Sanger sequencing was also performed to validate the mutation sites of the patient. Genetic harmfulness was predicted by multiple computational softwares, including SIFT Pred, Polyphen-2 HVAR Pred and MutationTaster Pred. Clinical characteristics of ALS induced by different MATR3 gene mutation sites were summarized by database retrieval.Results:The patient was a 69-year-old female, who began to show bulbar muscle weakness and then gradually developed to the facial muscles, including temporalis and masseter, and four limbs. In addition to the upper and lower motor neuron damage found in physical examination of the patient, the obvious facial muscle atrophy was also found in the patient. There was no family history of ALS in this patient. In terms of auxiliary examination, creatine kinase, rheumatism immunity and tumor markers were all normal. Cranial MRI showed no structural lesions and abnormal signals at the course of pyramidal tract. Electromyography suggested extensive neurogenic damage, decreased amplitude of repeated stimulation, abnormal measurement of blink reflex (BR) and skin sympathetic response (SSR). A heterozygous variant c.1472A>G (p.Y491C) of the MATR3 gene, which is a missense mutation, was detected in the patient. The variant was predicted as a harmful mutation by multiple computational softwares.Conclusions:A variant c.1472A>G (p.Y491C) of the MATR3 gene may be the pathogenic mutation of the patient. The patient not only has similar clinical manifestations to those of classic ALS, but also has facial muscle involvement. The electromyography shows abnormal SSR and BR.
ABSTRACT
BACKGROUND: Basal-like breast cancer (BLBC) or triple-negative breast cancer (TNBC) is an aggressive and highly metastatic subtype of human breast cancer. The present study aimed to elucidate the potential tumor-suppressive function of MATR3, an abundant nuclear protein, in BLBC/TNBC, whose cancer-relevance has not been characterized. METHODS: We analyzed in vitro tumorigenecity by cell proliferation and soft agar colony formation assays, apoptotic cell death by flow cytometry and Poly (ADP-ribose) polymerase (PARP) cleavage, epithelial-mesenchymal transition (EMT) by checking specific EMT markers with real-time quantitative PCR and in vitro migration and invasion by Boyden Chamber assays. To elucidate the underlying mechanism by which MATR3 functions as a tumor suppressor, we performed Tandem affinity purification followed by mass spectrometry (TAP-MS) and pathway analysis. We also scrutinized MATR3 expression levels in the different subtypes of human breast cancer and the correlation between MATR3 expression and patient survival by bioinformatic analyses of publicly available transcriptome datasets. RESULTS: MATR3 suppressed in vitro tumorigenecity, promoted apoptotic cell death and inhibited EMT, migration, and invasion in BLBC/TNBC cells. Various proteins regulating apoptosis were identified as MATR3-binding proteins, and YAP/TAZ pathway was suppressed by MATR3. MATR3 expression was inversely correlated with the aggressive and metastatic nature of breast cancer. Moreover, high expression levels of MATR3 were associated with a good prognosis of breast cancer patients. CONCLUSIONS: Our data demonstrate that MATR3 functions as a putative tumor suppressor in BLBC/TNBC cells. Also, MATR3 potentially plays a role as a biomarker in predicting chemotherapy-sensitivity and patient survival in breast cancer patients.