AUF1 Promotes Proliferation and Invasion of Thyroid Cancer Downregulation of ZBTB2 and Subsequent TRIM58.

The pathogenesis of papillary thyroid cancer (PTC), the most common type of thyroid cancer, is not yet fully understood. This limits the therapeutic options for approximately 7% of invasive PTC patients. The critical role of AUF1 in the progression of thyroid cancer was first reported in 2009, however, its molecular mechanism remained unclear.

HYOU1 facilitates proliferation, invasion and glycolysis of papillary thyroid cancer via stabilizing LDHB mRNA.

HYOU1 is upregulated in many kinds of cancer cells, and its high expression is associated with tumour invasiveness and poor prognosis. However, the role of HYOU1 in papillary thyroid cancer (PTC) development and progression remains to be elucidated. Here, we reported that HYOU1 was highly expressed in human PTC and associated with poor prognosis.

TRIM29 inhibits miR-873-5P biogenesis via CYTOR to upregulate fibronectin 1 and promotes invasion of papillary thyroid cancer cells.

Papillary thyroid cancer (PTC) is the most common endocrine tumor with an increasing incidence, has a strong propensity for neck lymph node metastasis. Limited treatment options are available for patients with advanced or recurrent metastatic disease, resulting in a poor prognosis. Tripartite motif protein 29 (TRIM29) is dysregulated in various cancer and functions as oncogene or tumor suppressor in discrete cancers.

BAG5 promotes invasion of papillary thyroid cancer cells via upregulation of fibronectin 1 at the translational level.

Papillary thyroid cancer (PTC), the most common thyroid malignancy, has a strong propensity for neck lymph node metastasis, which will increase the risk of local recurrence and decrease the survival in some high-risk groups. Hence, it is essential to set up a reliable biomarker to predict lymph node metastasis. BAG5 is a unique member of the BAG cochaperone family because it consists of more than one BAG domain, which acts as modulator of chaperone activity.

p53-dependent transcriptional suppression of BAG3 protects cells against metabolic stress via facilitation of p53 accumulation.

Solid tumour frequently undergoes metabolic stress during tumour development because of inadequate blood supply and the high nutrient expenditure. p53 is activated by glucose limitation and maintains cell survival via triggering metabolic checkpoint. However, the exact downstream contributors are not completely identified.

Sestrin 2 protects against metabolic stress in a p53-independent manner.

Glucose limitation activates p53, which functions as an adaptive response to maintain cell survival. However, p53 is frequently deleted or mutated in a variety of tumors, while most cancer cells can acclimatize themselves to metabolically unfavorable surrounding, indicating that alternative mechanisms other than p53 transactivation underly adaptive response of cancer cells with p53 deletion or mutation to metabolically hostile environment. Sestrin 2 (SESN2) is a p53 downstream target, which plays a protective role against various stressful stimuli, such as genotoxic, energetic, and oxidative stress.

Cathepsin D protects renal tubular cells from damage induced by high glucose independent of its enzymatic activity.

Although glomerular and vascular damage have been considered the main characteristics of diabetic kidney disease (DKD), accumulating data now indicate that tubular atrophy also plays a major role. Cathepsin D (CatD) is the major aspartate protease within lysosomes. The current study demonstrated that CatD expression was altered in the renal tubular epithelium in patients with diabetes mellitus (DM).

AUF1 modulates TGF-β signal in renal tubular epithelial cells via post-transcriptional regulation of Nedd4L expression.

Posttranscriptional regulation process plays important roles in renal disease pathogenesis. AU-rich element RNA-binding protein (AUF1) interacts with and destabilizes mRNAs containing AU-rich elements (AREs) in their 3'UTR. The current study demonstrated that AUF1 was increased in unilateral ureteral obstruction (UUO) animal models.

Induction of epithelial-mesenchymal transition (EMT) by Beclin 1 knockdown via posttranscriptional upregulation of ZEB1 in thyroid cancer cells.

Beclin 1 has emerged as a haploinsufficient tumor suppression gene in a variety of human carcinomas. In order to clarify the role of Beclin 1 in thyroid cancer, Beclin 1 was knockdown in thyroid cancer cell lines. The current study demonstrated that knockdown of Beclin 1 resulted in morphological and molecular changes of thyroid cancer cells consistent with epithelial-mesenchymal transition (EMT), a morphogenetic procedure during which cells lose their epithelial characteristics and acquire mesenchymal properties concomitantly with gene expression reprogramming.

BAG3 regulates ECM accumulation in renal proximal tubular cells induced by TGF-β1.

Previously we have demonstrated that Bcl-2-associated athanogene 3 (BAG3) is increased in renal fibrosis using a rat unilateral ureteral obstruction model. The current study investigated the role of BAG3 in renal fibrosis using transforming growth factor (TGF)-β1-treated human proximal tubular epithelial (HK-2) cells. An upregulation of BAG3 in vitro models was observed, which correlated with the increased synthesis of extracellular matrix (ECM) proteins and expression of tissue-type plasminogen activator inhibitor (PAI)-1.

Involvement of Nrf2 in proteasome inhibition-mediated induction of ORP150 in thyroid cancer cells.

Oxygen-regulated protein 150 (ORP150) is an inducible ER chaperone by numerous cellular insults and sustains cellular viability. We have previously reported that ORP150 is differentially induced in a panel thyroid cancer cells and represents as an unwanted molecular consequence during exposure to proteasome inhibition. However, the molecular basis for induction of ORP150 by proteasome inhibitors in thyroid cancer cells remains unclear.

BAG3 elevation inhibits cell proliferation via direct interaction with G6PD in hepatocellular carcinomas.

Bcl-2 associated athanogene 3 (BAG3) contains multiple protein-binding motifs to mediate potential interactions with chaperons and/or other proteins, which is possibly ascribed to the multifaceted functions assigned to BAG3. The current study demonstrated that BAG3 directly interacted with glucose 6 phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP). BAG3 suppressed the PPP flux, de novo DNA synthesis and cell growth in hepatocellular carcinomas (HCCs).

Cordyceps sinensis attenuates renal fibrosis and suppresses BAG3 induction in obstructed rat kidney.

BAG3 regulates a number of cellular processes, including cell proliferation, apoptosis, adhesion and migration, and epithelial-mesenchymal transition (EMT). However, the role of BAG3 in renal tubular EMT and renal interstitial fibrosis remains elusive. This study aimed to examine the dynamic expression of BAG3 during renal fibrosis, and to investigate the efficacy of Cordyceps sinensis (C.

Advanced glycation end products promote proliferation and suppress autophagy via reduction of Cathepsin D in rat vascular smooth muscle cells.

Autophagy is closely involved in vascular smooth muscle cell (VSMC) function, but little is known about the association between advanced glycation end products (AGEs) and autophagy and its role in AGEs-induced proliferation and migration of VSMCs. The current study investigated the effects of AGEs on the phenotypic modulation and autophagy of VSMCs, as well as the potential underlying mechanisms. Primary rat VSMCs were treated with bovine serum albumin or AGEs.

Implication of Bcl-2-associated athanogene 3 in fibroblast growth factor-2-mediated epithelial-mesenchymal transition in renal epithelial cells.

The epithelial-mesenchymal transition (EMT) of tubular epithelial cells to myofibroblast-like cells plays a substantial role in renal tubulointerstitial fibrosis, which is a common pathological character of end-stage renal disease (ESRD). Fibroblast growth factor-2 (FGF-2) triggers EMT in tubular epithelial cells and increases Bcl-2-associated athanogene 3 (BAG3) expression in neural progenitor and neuroblastoma cells. In addition, a novel role of regulation of EMT has been ascribed to BAG3 recently.

BAG3 promoted starvation-induced apoptosis of thyroid cancer cells via attenuation of autophagy.

Context: BAG3 plays a regulatory role in a number of cellular processes. Recent studies have attracted much attention on its role in activation of selective autophagy. In addition, we have very recently reported that BAG3 is implicated in a BECN1-independent autophagy, namely noncanonical autophagy.

BAG3 is upregulated by c-Jun and stabilizes JunD.

BAG3 plays a regulatory role in a number of cellular processes, including cell proliferation, apoptosis, adhesion and migration, epithelial-mesenchymal transition (EMT), autophagy activation, and virus infection. The AP-1 transcription factors are implicated in a variety of important biological processes including cell differentiation, proliferation, apoptosis and oncogenesis. Recently, it has been reported that AP-1 protein c-Jun inhibits autophagy and enhances apoptotic cell death mediated by starvation.

BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells.

Emerging lines of evidence have shown that blockade of ubiquitin-proteasome system (UPS) activates autophagy. The molecular players that regulate the relationship between them remain to be elucidated. Bcl-2 associated athanogene 3 (BAG3) is a member of the BAG co-chaperone family that regulates the ATPase activity of heat shock protein 70 (HSP70) chaperone family.

Beclin 1 enhances proteasome inhibition-mediated cytotoxicity of thyroid cancer cells in macroautophagy-independent manner.

Context: The ubiquitin-proteasome system and macroautophagy are two major pathways for intracellular protein degradation. Emerging lines of evidence have shown that blockade of ubiquitin-proteasome system by proteasome inhibitors activates macroautophagy.

Objective: The purpose of this study was to determine the involvement of autophagy essential gene Beclin 1 in cytotoxicity of thyroid cancer cells mediated by proteasome inhibitors.

Implication of Nrf2 and ATF4 in differential induction of CHOP by proteasome inhibition in thyroid cancer cells.

Proteasome inhibition may cause endoplasmic reticulum (ER) stress, which has been reported to be implicated in the antitumoral effects of proteasome inhibitors. CCAAT/enhancer-binding protein homologous protein (CHOP) is induced by a variety of adverse physiological conditions including ER stress and is involved in apoptosis. We have reported that distinct induction of CHOP contributes to the responsiveness of thyroid cancer cells to proteasome inhibitors.

Resveratrol prevents TNFα-induced suppression of adiponectin expression via PPARγ activation in 3T3-L1 adipocytes.

Tumor necrosis factor α (TNFα) is an adipokine, whose increase is known to suppress the expression and secretion of adiponectin in adipocytes. Resveratrol has been ever reported to recover the suppression of adiponectin by TNFα, but the underlying mechanism remains poorly understood. In this study, we validated the roles of resveratrol in the inhibition of the adiponectin by TNFα in 3T3-L1 cells.

Involvement of JNK and NF-κB pathways in lipopolysaccharide (LPS)-induced BAG3 expression in human monocytic cells.

Lipopolysaccharide (LPS) is an outer-membrane glycolipid component of Gram-negative bacteria known for its fervent ability to activate monocytic cells and for its potent proinflammatory capabilities. Bcl-2-associated athanogene 3 (BAG3) is a survival protein that has been shown to be stimulated during cell response to stressful conditions, such as exposure to high temperature, heavy metals, proteasome inhibition, and human immunodeficiency virus 1 (HIV-1) infection. In addition, BAG3 regulates replication of Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) replication, suggesting that BAG3 could participate in the host response to infection.

Resveratrol protects leukemic cells against cytotoxicity induced by proteasome inhibitors via induction of FOXO1 and p27Kip1.

Background: It was reported recently that resveratrol could sensitize a number of cancer cells to the antitumoral effects of some conventional chemotherapy drugs. The current study was designed to investigate whether resveratrol could sensitize leukemic cells to proteasome inhibitors.

Methods: Leukemic cells were treated with MG132 alone or in combination with resveratrol.

Proteasome inhibition induces a p38 MAPK pathway-dependent antiapoptotic program via Nrf2 in thyroid cancer cells.

Context: Our previous data showed that reactive oxygen species generation might be ascribed to the cytotoxic response of thyroid cancer cells to proteasome inhibition and the ability of cancer cells to induce catalytic subunit for glutamate cysteine ligase (GCLC) and subsequent production of glutathione, thereby scavenging reactive oxygen species was partly ascribed to the cytotoxic responses of thyroid cancer cells to proteasome inhibition. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor responsible for transcriptional activation of various cytoprotective genes including GCLC.

Objective: The purpose of this study was to determine the involvement of Nrf2 in GCLC induction and cytotoxicity of thyroid cancer cells mediated by proteasome inhibition.