FAM210B activates STAT1/IRF9/IFIT3 axis by upregulating IFN-α/β expression to impede the progression of lung adenocarcinoma.

FAM210B (family with sequence similarity 210 member B) is a novel protein that has been linked to tumor development. However, its role and underlying mechanisms in lung adenocarcinoma (LUAD) progression remain largely unexplored. In this study, FAM210B was observed to be down-regulated in LUAD cells.

TRIAL-based combination therapies in cancers.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows promising therapeutic potential in cancer treatment as it is able to trigger extrinsic apoptotic pathways by binding to the cognate death receptor, causing broad-spectrum apoptosis in cancer cells with negligible toxicity to normal cells. However, the majority of cancers display resistance to TRAIL, limiting its clinical utility. Overcoming resistance to TRAIL therapies remains a challenge in the development of effective anti-cancer strategies.

Ferroptosis in cancer (Review).

Ferroptosis is a type of programmed cell death depending on iron and reactive oxygen species. This unique cell death process has attracted a great deal of attention in the field of cancer research over the past decade. Research on the association of ferroptosis signal pathways and cancer development indicated that targeting ferroptosis has great potential for cancer therapy.

Artesunate induces ferroptosis by regulating MT1G and has an additive effect with doxorubicin in diffuse large B-cell lymphoma cells.

Diffuse Large B-cell lymphoma (DLBCL) is a highly aggressive disease with heterogeneous outcomes and marked variability in the response to chemotherapy. DLBCL comprises two major subtypes: germinal centre B-cell-like (GCB) and activated B-cell-like (ABC). Our study highlights the extensive antitumour activity of artesunate (ART) against both major DLBCL subtypes.

Exosomal PPARγ derived from macrophages suppresses LPS-induced peritonitis by negative regulation of CD14/TLR4 axis.

Background: Intercellular communication between macrophages and peritoneal mesothelial cells (PMCs) has been suggested as a key factor regulating peritonitis development. Here, we explored whether PPARγ (peroxisome proliferator-activated receptor gamma) can be packaged into macrophage exosomes to mediate intercellular communication and regulate peritonitis.

Methods: Macrophage exosomes were isolated by ultracentrifugation and identified by nanoparticle tracking analysis and transmission electron microscopy.

Polyphyllin D punctures hypertrophic lysosomes to reverse drug resistance of hepatocellular carcinoma by targeting acid sphingomyelinase.

Hypertrophic lysosomes are critical for tumor progression and drug resistance; however, effective and specific lysosome-targeting compounds for cancer therapy are lacking. Here we conducted a lysosomotropic pharmacophore-based in silico screen in a natural product library (2,212 compounds), and identified polyphyllin D (PD) as a novel lysosome-targeted compound. PD treatment was found to cause lysosomal damage, as evidenced by the blockade of autophagic flux, loss of lysophagy, and the release of lysosomal contents, thus exhibiting anticancer effects on hepatocellular carcinoma (HCC) cell both in vitro and in vivo.

GSK3β/ITCH/c-FLIP Axis Counteracts TRAIL-induced Apoptosis in Human Lung Adenocarcinoma Cells.

Aims: Further investigation on the mechanism of action of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in NSCLC would shed light on the understanding of TRAIL resistance and provide new clues for the counter-strategy.

Background: Cellular FLICE-inhibitory protein (c-FLIP) is a critical inhibitor of TRAIL-induced apoptosis. Our previous study suggested that glycogen synthase kinase 3β (GSK3β) positively regulated c-FLIP expression in human lung adenocarcinoma cells.

ZSWIM1 Promotes the Proliferation and Metastasis of Lung Adenocarcinoma Cells through the STK38/MEKK2/ERK1/2 Axis.

Investigating the functions of the proteins with no or less functional annotations is an important goal of the HPP (Human Proteome Project) Grand Project. In this study, we investigated the function of such a protein, ZSWIM1 (C20orf162), its gene located on chromosome 20. Its expression is upregulated in lung adenocarcinoma compared with the adjacent normal tissues and negatively correlated with the overall survival.

DDX17 promotes the growth and metastasis of lung adenocarcinoma.

DEAD box RNA helicase 17 (DDX17) has been shown to be an RNA binding protein involved in RNA metabolism and associated with cancer progression. However, the biological role of DDX17 in the pathogenesis of lung adenocarcinoma (LUAD) has not been well characterized. Here, we demonstrated that DDX17 promoted the proliferation, migration and invasion of H1299 and A549 lung adenocarcinoma cells.

3'untranslated regions (3'UTR) of mRNA displays anticancer effects in non-small cell lung cancer (NSCLC) cells.

RNA-based therapeutics has attracted substantial interest from both academics and pharmaceutical companies. In this study, we investigated the function and the underlying mechanism of 3'UTR in NSCLC H1299 and A549 cells. We found that transfected plasmids significantly increased the proliferation, migration and invasion of NSCLC cells, whereas 3'UTR could suppress the promotional effect of GSN protein on the development of NSCLC .

ANXA1-GSK3β interaction and its involvement in NSCLC metastasis.

Although initially discovered and extensively studied for its role in inflammation, Annexin A1 (ANXA1) has been reported to be closely related to cancer in recent years, and its role in cancer is specific to tumor types and tissues. In the present study, we identified ANXA1 as an interaction partner of glycogen synthase kinase 3 beta (GSK3β), a multi-functional serine/threonine kinase tightly associated with cell fate determination and cancer, and assessed the functional significance of GSK3β-ANXA1 interaction in the metastasis of non-small cell lung cancer (NSCLC). We confirmed the interaction between GSK3β and ANXA1 in vitro and in H1299 and A549 cells by Glutathione-S-transferase (GST) pull-down assay and co-immunoprecipitation.

TRIM21-regulated Annexin A2 plasma membrane trafficking facilitates osteosarcoma cell differentiation through the TFEB-mediated autophagy.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, which is characterized by dysfunctional autophagy and poor differentiation. Our recent studies have suggested that the tripartite motif containing-21 (TRIM21) plays a crucial role in regulating OS cell senescence and proliferation via interactions with several proteins. Yet, its implication in autophagy and differentiation in OS is largely unknown.

Cytoplasmic PCNA is located in the actin belt and involved in osteoclast differentiation.

Osteoporosis (OP) is an age-related osteolytic disease and characterized by low bone mass and more prone to fracture due to active osteoclasts. Proliferating cell nuclear antigen (PCNA) has been long identified as a nuclear protein playing critical roles in the regulation of DNA replication and repair. Recently, a few studies have demonstrated the cytoplasmic localization of PCNA and its function associated with apoptosis in neutrophil and neuroblastoma cells.

The emerging roles of hnRNPK.

Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an DNA/RNA-binding protein and regulates a wide range of biological processes and disease pathogenesis. It contains 3 K-homologous (KH) domains, which are conserved in other RNA-binding proteins, mediate nucleic acid binding activity, and function as an enhancer or repressor of gene transcription. Phosphorylation of the protein alters its regulatory function, which also enables the protein to serve as a docking platform for the signal transduction proteins.

YAP mediates the positive regulation of hnRNPK on the lung adenocarcinoma H1299 cell growth.

Lung cancer is the leading cause of cancer death worldwide, and non-small cell lung cancer (NSCLC) accounts for 80%-85% of diagnostic cases. The molecular mechanisms of NSCLC pathogenesis are not well understood. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional protein that regulates gene expression and signal transduction and closely associated with tumorigenesis, but its mechanism of action in the pathogenesis of NSCLC is unclear.

Regulation and related mechanism of GSN mRNA level by hnRNPK in lung adenocarcinoma cells.

Gelsolin (GSN) is an actin filament-capping protein that plays a key role in cell migration. Here we show that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulates GSN expression level by binding to the 3'-untranslated region (3'UTR) of GSN mRNA in non-small cell lung cancers (NSCLC) H1299 cells which are highly metastatic and express high level of GSN. We found that hnRNPK overexpression increased the mRNA and protein level of GSN, whereas hnRNPK knockdown by siRNA decreased the mRNA and protein level of GSN in both H1299 and A549 cells, indicating a positive role of hnRNPK in the regulation of GSN expression.

hnRNPK modulates selective quality-control autophagy by downregulating the expression of HDAC6 in 293 cells.

hnRNPK modulates selective quality-control autophagy bAbstract. A recent study has reported that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulated autophagy in leukemia cells. However, the underlying mechanism of this remains elusive.

The flightless I protein interacts with RNA-binding proteins and is involved in the genome-wide mRNA post-transcriptional regulation in lung carcinoma cells.

The flightless I protein (FLII) belongs to the gelsolin family. Its function has been associated with actin remodeling, embryonic development, wound repair, and more recently with cancer. The structure of FLII is characterized by the N-terminal leucine-rich repeats (LRR) and C-terminal gesolin related repeated units that are both protein-protein inter-action domains, suggesting that FLII may exert its function by interaction with other proteins.

PKCα-GSK3β-NF-κB signaling pathway and the possible involvement of TRIM21 in TRAIL-induced apoptosis.

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a highly promising therapeutic agent for cancer treatment, owing to its ability to selectively target tumor cells for cell death while having little effect on most normal cells. However, recent research has found that many cancers, including non-small cell lung cancer (NSCLC), display resistance to TRAIL. Therefore, it is important to elucidate the molecular mechanisms governing the resistance of tumor cells to TRAIL treatment.

Proper autophagy is indispensable for angiogenesis during chick embryo development.

People have known that autophagy plays a very important role in many physiological and pathological events. But the role of autophagy on embryonic angiogenesis still remains obscure. In this study, we demonstrated that Atg7, Atg8 and Beclin1 were expressed in the plexus vessels of angiogenesis at chick yolk sac membrane and chorioallantoic membrane.

hnRNPK inhibits GSK3β Ser9 phosphorylation, thereby stabilizing c-FLIP and contributes to TRAIL resistance in H1299 lung adenocarcinoma cells.

c-FLIP (cellular FLICE-inhibitory protein) is the pivotal regulator of TRAIL resistance in cancer cells, It is a short-lived protein degraded through the ubiquitin/proteasome pathway. The discovery of factors and mechanisms regulating its protein stability is important for the comprehension of TRAIL resistance by tumor cells. In this study, we show that, when H1299 lung adenocarcinoma cells are treated with TRAIL, hnRNPK is translocated from nucleus to cytoplasm where it interacts and co-localizes with GSK3β.

[Interaction of Flightless I with Nup88 and Importin β].

High expression of Fightless I (FLII) is associated to multiple tumors. Based on our previous study that FLII might be involved in the nuclear export, we assessed the possible interaction of FLII with the nuclear envelop associating proteins Importin β and Nup88. We first constructed GST-FLII, GST-LRR recombinant plasmids and transformed them into the Rosetta strain to produce GST-FLII, GST-LRR fusion protein.

Cytoplasmic hnRNPK interacts with GSK3β and is essential for the osteoclast differentiation.

Osteoclast differentiation is a complex and finely regulated physiological process that involves a variety of signaling pathways and factors. Recent studies suggested that the Ser9 phosphorylation of Glycogen synthase kinase-3β (GSK3β) is required for the osteoclast differentiation. However, the precise underlying mechanism remains unclear.

A homogeneous time-resolved fluorescence-based high-throughput screening for discovery of inhibitors of Nef-sdAb19 interaction.

The human immunodeficiency virus (HIV) protein negative factor (Nef) is important for AIDS pathogenesis. An anti-Nef single-domain antibody (sdAb19) derived from camelids has been previously generated and shown to effectively block the physiological functions of Nef in vitro and in vivo in nef-transgenic mice. However, sdAb19 must be ectopically expressed within the target cell to be able to exert its neutralizing effect on Nef, while the extra-cellular administration method turned out to be ineffective.

14-3-3ζ reduces DNA damage by interacting with and stabilizing proliferating cell nuclear antigen.

Proliferating cell nuclear antigen (PCNA) is a processivity factor of DNA replication which plays critical roles in the regulation of DNA replication and repair. In this study, we show that PCNA interacts directly in vitro and in cells with 14-3-3ζ, an adaptor protein that regulates cell growth and response to DNA damage in eukaryotes. The interaction is mediated by at least two PCNA-binding sites on 14-3-3ζ, one of which is a novel non-canonical PIP (PCNA interacting protein) box.