Loss of STAG2 causes aneuploidy in normal human bladder cells

Abstract

ABSTRACT. The aim of this study was to determine how the function of human stromal antigen 2 (STAG2) plays an important role in proper chromosome separation. STAG2 mRNA in normal bladder cells and bladder tumor cells was evaluated by RT-PCR. The protein levels of STAG2 in normal bladder cells and bladder tumor cells were determined Loss of STAG2 function in cells by western blot. A cell proliferation assay was used to measure the growth of tumor cells and STAG2-inhibited normal cells, and STAG2-inhibited normal cells were subjected to karyotype analysis. Both STAG-2 mRNA and protein expression levels were lower in bladder cancer cells compared to the controls. Knockdown of STAG2 caused aneuploidy in normal bladder cells, leading to a decreased expression of the cohesin complex components SMC1, SMC3 and RAD21, but there was no obvious effect of STAG2 knockdown on cell proliferation. Our study indicated that abnormal expression of STAG2 could cause aneuploidy in normal bladder cells.

Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms

“…Another process cohesin is known to play a role in is DNA damage repair (Watrin and Peters, 2006). At this moment, no consensus exists on whether mutations in cohesin in human malignancies lead to genomic instability (Solomon et al, 2011;Balbás-Martínez et al, 2013;Li et al, 2015), although using our cohesin knockdown cells we did not observe changes of the overall karyotype. Similarly, human AML samples carrying cohesin mutations do in the affected animals, further supporting that Smc1a silencing promotes a clinical picture consistent with an MPN.…”

Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms

“…Another process cohesin is known to play a role in is DNA damage repair ( Watrin and Peters, 2006 ). At this moment, no consensus exists on whether mutations in cohesin in human malignancies lead to genomic instability ( Solomon et al, 2011 ; Balbás-Martínez et al, 2013 ; Li et al, 2015 ), although using our cohesin knockdown cells we did not observe changes of the overall karyotype. Similarly, human AML samples carrying cohesin mutations do not have an overt genomic instability phenotype ( Cancer Genome Atlas Research Network, 2013 ).…”

Embryonic atrazine exposure alters zebrafish and human miRNAs associated with angiogenesis, cancer, and neurodevelopment

“…PIMI has a known function of regulating cell cycle progression from late G1 through S-phase. In addition, STAG2 , TOP1 , and MAD2L2 were also miRNA targets that are involved in cell cycle processes including formation of the cohesion complex which is necessary for the separation of sister chromatids, alterations of topologic states, and accurate mitosis (Li et al, 2015; Listovsky et al, 2013; Xu et al, 2015). One limitation of the targeting analysis is that the samples analyzed in the current study and in the past transcriptomic analysis was from different biological samples.…”