Auf1

Decorin (DCN), a member of the small leucine-rich proteoglycan gene family, is secreted from stromal fibroblasts with non-cell-autonomous anti-breast-cancer effects. Therefore, in the present study, we sought to elucidate the function of decorin in breast stromal fibroblasts (BSFs). We first showed DCN downregulation in active cancer-associated fibroblasts (CAFs) compared to their adjacent tumor counterpart fibroblasts at both the mRNA and protein levels. Interestingly, breast cancer cells and the recombinant IL-6 protein, both known to activate fibroblasts in vitro, downregulated DCN in BSFs...

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment, significantly curtailing the efficacy of these treatments and, in some cases, resulting in fatal consequences. Despite identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis, the paucity of effective treatments for such damage is evident. In our study, we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells, thereby fortifying the integrity of the intestinal mucus barrier...

Arsenic (As), a common environmental pollutant, has become a hot topic in recent years due to its potentially harmful effects. Liver damage being a central clinical feature of chronic arsenic poisoning. However, the underlying mechanisms remain unclear. We demonstrated that arsenic can lead to oxidative stress in the liver and result in structural and functional liver damage, significantly correlated with the expression of AUF1, Dicer1, and miR-155 in the liver. Interestingly, knockdown AUF1 promoted the up-regulatory effects of arsenic on Dicer1 and miR-155 and the inhibitory effects on SOD1, which exacerbated oxidative damage in rat liver...

Metastatic progression is the primary cause of mortality in prostate cancer (PCa) patients. Although circular RNAs (circRNAs) have been implicated in cancer progression and metastasis, our current understanding of their role in PCa metastasis remains limited. In this study, we identified that circUBE3A (2,3,4,5), which originated from exons 2, 3, 4 and 5 of the human ubiquitin-protein ligase E3A (UBE3A) gene, was specifically downregulated in PCa tissues and correlated with the Gleason score, bone metastasis, and D'Amico risk classification...

Nickel pollution is a recognized factor contributing to lung cancer. Understanding the molecular mechanisms of its carcinogenic effects is crucial for lung cancer prevention and treatment. Our previous research identified the downregulation of a long noncoding RNA, maternally expressed gene 3 (MEG3), as a key factor in transforming human bronchial epithelial cells (HBECs) into malignant cells following nickel exposure. In our study, we found that deletion of MEG3 also reduced the expression of RhoGDIβ...

Selective pressures on viruses provide opportunities to establish target site specificity and mechanisms of antivirals. Enterovirus (EV)-A71 with resistant mutations in the stem loop (SL) II internal ribosome entry site (IRES) (SLIIresist ) were selected at low doses of the antiviral dimethylamiloride (DMA)-135. The EV-A71 mutants were resistant to DMA-135 at concentrations that inhibit replication of wild-type virus. EV-A71 IRES structures harboring resistant mutations induced efficient expression of Luciferase messenger RNA in the presence of noncytotoxic doses of DMA-135...

Cells encounter a variety of stresses throughout their lifetimes. Oxidative stress can occur via a myriad of factors, including exposure to chemical toxins or UV light. Importantly, these stressors induce chemical changes (e.g. chemical modifications) to biomolecules, such as RNA. Commonly, guanine is oxidized to form 8-oxo-7,8-hydroxyguanine (8-oxoG) and this modification can disrupt a plethora of cellular processes including messenger RNA translation and stability. Polynucleotide phosphorylase (PNPase), heterogeneous nuclear ribonucleoprotein D (HNRPD/Auf1), poly(C)-binding protein (PCBP1/HNRNP E1), and Y-box binding protein 1 (YB-1) have been identified as four RNA-binding proteins that preferentially bind 8-oxoG-modified RNA over unmodified RNA...

Alpha-synuclein (SNCA) accumulation plays a central role in the pathogenesis of Parkinson's disease. Determining and interfering with the mechanisms that control SNCA expression is one approach to limiting disease progression. Currently, most of our understanding of SNCA regulation is protein-based. Post-transcriptional mechanisms directly regulating SNCA mRNA expression via its 3' untranslated region (3'UTR) were investigated here. Mass spectrometry of proteins pulled down from murine brain lysates using a biotinylated SNCA 3'UTR revealed multiple RNA-binding proteins, of which HNRNPD/AUF1 was chosen for further analysis...

HnRNPs are ubiquitously expressed RNA-binding proteins, tightly controlling posttranscriptional gene regulation. Consequently, hnRNP networks are essential for cellular homeostasis and their dysregulation is associated with cancer and other diseases. However, the physiological function of hnRNPs in non-cancerous cell systems are poorly understood. We analyzed the importance of HNRNPDL in endothelial cell functions. Knockdown of HNRNPDL led to impaired proliferation, migration and sprouting of spheroids. Transcriptome analysis identified cyclin D1 ( CCND1 ) and tropomyosin 4 ( TPM4 ) as targets of HNRNPDL, reflecting the phenotypic changes after knockdown...

In a recent study, Liu and colleagues demonstrated a role for the purine biosynthesis enzyme ATIC and its substrate in regulating the protein levels of the Parkinson's disease kinase LRRK2, which rescues neurodegeneration and neuroinflammation in distinct animal models. This work highlights a novel avenue to target LRRK2 protein levels as a strategy to prevent neurodegeneration in Parkinson's disease.

Circular RNAs (circRNAs) play an important role in regulating the development of human cancers through diverse biological functions. However, the exact molecular mechanisms underlying the role of circRNAs in papillary thyroid cancer (PTC) remain largely unknown. Here, we found that hsa_circ_0011385, designated as circular eukaryotic translation initiation factor 3 subunit I (circEIF3I), preferentially localized in the cytoplasm of PTC cells and was more stable than its linear counterpart, EIF3I. Gain- and loss-of-function studies indicated that circEIF3I promoted PTC progression by facilitating cell proliferation, cell cycle, cell migration, and invasion in vitro, as well as PTC cell proliferation in vivo...

BACKGROUND: Increasing evidences has indicated that primary and acquired resistance of ovarian cancer (OC) to platinum is mediated by multiple molecular and cellular factors. Understanding these mechanisms could promote the therapeutic efficiency for patients with OC. METHODS: Here, we screened the expression pattern of circRNAs in samples derived from platinum-resistant and platinum-sensitive OC patients using RNA-sequencing (RNA-seq). The expression of hsa_circ_0010467 was validated by Sanger sequencing, RT-qPCR, and fluorescence in situ hybridization (FISH) assays...

Mutations in LRRK2 are the most common genetic causes of Parkinson's disease (PD). While the enzymatic activity of LRRK2 has been linked to PD, previous work has also provided support for an important role of elevated LRRK2 protein levels, independent of enzymatic activity, in PD pathogenesis. However, the mechanisms underlying the regulation of LRRK2 protein levels remain unclear. Here, we identify a role for the purine biosynthesis pathway enzyme ATIC in the regulation of LRRK2 levels and toxicity. AICAr, the precursor of ATIC substrate, regulates LRRK2 levels in a cell-type-specific manner in vitro and in mouse tissue...

Repetitive ischemia with reperfusion (I/R) injury is a common cause of myalgia. I/R injuries occur in many conditions that differentially affect males and females including complex regional pain syndrome and fibromyalgia. Our preclinical studies have indicated that primary afferent sensitization and behavioral hypersensitivity due to I/R may be due to sex specific gene expression in the DRGs and distinct upregulation of growth factors and cytokines in the affected muscles. In order to determine how these unique gene expression programs may be established in a sex dependent manner in a model that more closely mimics clinical scenarios, we utilized a newly developed prolonged ischemic myalgia model in mice whereby animals experience repeated I/R injuries to the forelimb and compared behavioral results to unbiased and targeted screening strategies in male and female DRGs...

BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogeneous cluster of hematologic malignancies. Leukemic stem cells (LSCs) are one of the culprits for the persistence and relapse of AML. The discovery of copper-induced cell death, namely cuproptosis, gives bright insights into the treatment of AML. Analogous to copper ions, long non-coding RNAs (lncRNAs) are not bystanders for AML progression, especially for LSC physiology. Uncovering the involvement of cuproptosis-related lncRNAs in AML will benefit clinical management...

The effector complex of RNA interference (RNAi) contains at its core an ARGONAUTE (AGO) protein bound to a small guide RNA. AGO proteins adopt a two-lobed structure in which the N-terminal (N) and Piwi-Argonaute-Zwille (PAZ) domains make up one lobe, while the middle (MID) and Piwi domains make up the other. Specific biochemical functions of PAZ, MID and Piwi domains of eukaryotic AGO proteins have been described, but the functions of the N domain remain less clear. Here, we use yeast two-hybrid screening with the N domain of the founding member of the AGO protein family, arabidopsis AGO1, to reveal that it interacts with many factors involved in regulated proteolysis...

Emerging evidence shows that the microRNA-141-3p is involved in various age-related pathologies. Previously, our group and others reported elevated levels of miR-141-3p in several tissues and organs with age. Here, we inhibited the expression of miR-141-3p using antagomir (Anti-miR-141-3p) in aged mice and explored its role in healthy aging. We analyzed serum (cytokine profiling), spleen (immune profiling), and overall musculoskeletal phenotype. We found decreased levels of pro-inflammatory cytokines (such as TNF-α, IL-1β, IFN-γ) in serum with Anti-miR-141-3p treatment...

In this study, it is found that the lncRNA, DNA damage inducible transcript 4 antisense RNA1 (DDIT4-AS1), is highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues due to H3K27 acetylation in the promoter region, and promotes the proliferation, migration, and invasion of TNBC cells via activating autophagy. Mechanistically, it is shown that DDIT4-AS1 induces autophagy by stabilizing DDIT4 mRNA via recruiting the RNA binding protein AUF1 and promoting the interaction between DDIT4 mRNA and AUF1, thereby inhibiting mTOR signaling pathway...

BACKGROUND: The target genes of AU-rich Element RNA-binding Protein 1 (AUF1), which is an RNA binding protein, and its role in the progression of hepatocellular carcinoma (HCC) is still elusive. This study aims to investigate the biological function and the underlying target genes of AUF1 in HCC. METHODS: RNA sequencing data and the Liver Cancer Institute (LCI) database were used to screen candidate targets of AUF1. LCI database, TCGA database, and a retrospective HCC cohort were used to investigate the correlation between AUF1 and alpha-fetoprotein (AFP) and their prognostic values in HCC patients...

AIMS: The existence of modified rNMPs embedded in genomic DNA, as a consequence of oxidative stress conditions, including 8-oxo-guanosine and ribose monophosphate abasic site (rAP), has been recently highlighted by several works including ours. Although the activity of APE1, a key enzyme of the base excision repair pathway, in the repair of rAP sites results as efficient as the canonical deoxyribose monophosphate abasic sites (dAP), its incision repair activity on 8-oxo-guanosine is very weak...