Tumor suppressive function of Matrin 3 in the basal-like breast cancer

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.

Oxidative Stress- and Autophagy-Inducing Effects of PSI-LHCI from Botryococcus braunii in Breast Cancer Cells

“…We proceeded to choose the concentration point closest to the IC 50 value (12.5 µg/mL PSI-LHCI, *** p < 0.01) revealed after exposure of MDA-MB-231 cells to PSI-LHCI following 24 h of incubation. Our results confirmed that PSI-LHCI induces a decrease in cell viability in the triple-negative breast cancer cell line, MDA-MB-231, with superior results than the well-known cancer cell line positive control Staurosporine [47].…”

“…A prestained protein standard was used to estimate PSI-LHCI and co-eluting components (~3.5-260 kDa). Two-dimensional (2D) native/SDS-PAGE polypeptide spots indicated a high abundance of PSI-LHCI complex components and subunits as observed in previous reports providing an assessment of the polypeptide composition of our preparation [28,47]. Although we notice a small contribution of LHCII, a mobile antenna, judging from our 77 K fluorescence assay, it is not deemed a major contributor [34,35].…”

Matrin3 regulates cell proliferation and spindle dynamics by regulating CDC14B alternative splicing

“…Other studies also observed that Matrin3 loss results in reduced cell proliferation 24,25,46 and suggested increased apoptosis as a cause. Our data indicate that at least in CRC cells, Matrin3 depletion results in alterations in microtubule dynamics, possibly leading to reduced cell proliferation as studies had shown that the stabilization of microtubules inhibit cell proliferation [47][48][49] .…”

“…The impaired formation of dynamic nuclear condensates due to ALS-associated mutations in Matrin3 possibly contributes to its pathogenic mechanism 22 . There is conflicting evidence for a role of Matrin3 in cancer with some studies indicating a potential role of Matrin3 as an oncogene and other studies suggesting a tumor suppressive function [23][24][25] . Although many different Matrin3 RNA targets were catalogued [11][12][13] , it remains unclear which of these specific targets mediate Matrin3 function and contribute to the observed phenotypes of Matrin3 in different cells and tissues.…”

OTUD6A Is an Aurora Kinase A-Specific Deubiquitinase

“…Western blotting was performed as described [ 52 ]. The cells were lysed in RIPA buffer supplemented with protease and phosphatase inhibitors (GenDepot, Houston, TX, USA).…”