TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization

Abstract

Neuroblastoma is the most common solid tumor in childhood and represents 15% of all children’s cancer deaths. We have previously demonstrated that tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite totif (TRIM) protein family, has significant effects on neuroblastoma proliferation and migration in vitro and tumorigenicity in vivo. However, the mechanism by which this putative tumor suppressor influences cell proliferation and tumorigenicity was undetermined. Here we show, for the first time, TRIM16’s striking pattern of expression and dynamic localization during cell cycle progression and neuroblastoma tumor development. In a tyrosine hydroxylase MYCN (TH-MYCN) neuroblastoma mouse model, immunohistochemical staining revealed strong nuclear TRIM16 expression in differentiating ganglia cells but not in the tumor-initiating cells. Furthermore in vitro studies clearly demonstrated that during G1 cell cycle phase, TRIM16 protein expression is upregulated and shifts to the nucleus of cells. TRIM16 also plays a role in cell cycle progression through changes in Cyclin D1 and p27 expression. Importantly, using TRIM16 deletion mutants, an uncharacterized protein domain of TRIM16 was found to be required for both TRIM16’s growth inhibitory effects and its nuclear localization. Taken together, our data suggest that TRIM16 acts as a novel regulator of both neuroblastoma G1/S progression and cell differentiation.

Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition

“…Another estrogen-responsive protein, TRIM16, which inhibits hepatocellular carcinoma cell migration and invasion by suppression of ZEB2 expression as well as suppresses cancer cell viability by involving interaction and stabilization of TDP43 with consequent eff ects on E2F1 and pRb proteins (Kim et al 2016), is also up-regulated in glioma cells without IRE1 signaling enzyme function. Moreover, TRIM16 inhibits neuroblastoma cells proliferation through cell cycle regulation and induces apoptosis via activation of caspase-2 (Bell et al 2013;Kim et al 2013). Th erefore, our results conform to data that FAM162A, PGRMC2, TRIM16, and SLC39A6 have mainly anti-proliferative functions through interaction with diff erent transcription coregulators and signaling pathways of ER stress in cell specifi c manner.…”

“…Moreover, recently was shown that TRIM16 inhibits cancer cell viability by a novel mechanism involving interaction and stabilization of TDP43 with consequent eff ects on E2F1 and pRb proteins (Kim et al 2016). Th ere is also data that TRIM16 inhibits neuroblastoma cells proliferation through cell cycle regulation and melanoma cells proliferation and migration through regulation of interferon beta 1 as well as induces apoptosis through activation of caspase-2 in cancer cells (Bell et al 2013;Kim et al 2013;Sutton et al 2014).…”

Upregulation of MG53 Induces Diabetic Cardiomyopathy Through Transcriptional Activation of Peroxisome Proliferation-Activated Receptor α

“…45 Some other members travel between the cytosol and nucleus to exert their functions. 46,47 In this study, we have found that the expression of MG53 is markedly increased in several animal models with metabolic disorders, although the underlying mechanism remains elusive. Candidate mechanisms may include changes in nutrients or genetic defects, or dysregulation of transcription factors or noncoding RNAs under pathological conditions.…”

Long Non-Coding RNA LUCAT1 Promotes Proliferation and Invasion in Clear Cell Renal Cell Carcinoma Through AKT/GSK-3β Signaling Pathway

“…The unlimited proliferation of cancer cells is often due to disorders of the cell cycle [23,24]. Our research team previously reported that knockdown of lncRNA AATBC resulted in inhibited bladder cancer cell proliferation through cell cycle arrest [25].…”