Arid5a, an RNA-Binding Protein in Immune Regulation: RNA Stability, Inflammation, and Autoimmunity

Nyati, Kishan Kumar; Zaman, Mohammad Mahabub-Uz; Sharma, Praveen; Kishimoto, Tadamitsu

doi:10.1016/j.it.2020.01.004

Cited by 46 publications

(46 citation statements)

References 79 publications

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“…[19,20] Inflammatory cytokines in the microenvironment of tumor cells are also relevant to the tumor immune escape. [21] Non-steroidal antiinflammatory drugs (NSAIDs) have shown therapeutic potentials against several cancers including BC, [6] and some of them could reduce cancer risks and mortality. [22] Multiple mechanisms were implicated in the effects of NSAIDs on BC,s uch as inhibition of COXa nd blockade of prostaglandin cascade.…”

Section: Introductionmentioning

confidence: 99%

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Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

et al. 2020

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Breast cancer (BC) is one of the most common malignancies in women and often accompanied by inflammatory processes.Cyclooxygenase-2 (COX-2) playsavital role in the progression of BC,c orrelating with the expression of programmed death-ligand 1(PD-L1). Overexpression of PD-L1 contributes to the immune escape of cancer cells,a nd its blockade would stimulate anticancer immunity.T wo multispecific platinum(IV) complexes DNP and NP were prepared using non-steroidal antiinflammatory drug naproxen (NPX) as axial ligand(s) to inhibit the BC cells.D NP exhibited high cytotoxicity and antiinflammatory properties superior over NP, cisplatin and NPX;m oreover,i td isplayed potent antitumor activity and almost no general toxicity in mice bearing triplenegative breast cancer (TNBC). Mechanistic studies revealed that DNP could downregulate the expression of COX-2 and PD-L1 in vitro and vivo,inhibit the secretion of prostaglandin, reduce the expression of BC-associated protein BRD4 and phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), and block the oncogene c-Myc in BC cells.T hese findings demonstrate that DNP is capable of intervening in inflammatory,i mmune,a nd metastatic processes of BC,t hus presenting anew mechanism of action for anticancer platinum-(IV) complexes.T he multispecificity offers as pecial superiority for DNP to treat TNBC by combining chemotherapyand immunotherapyi none molecule.

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Section: Introductionmentioning

confidence: 99%

“…Recently, suppression of proto‐oncogene c‐Myc was also shown to decrease the expression of PD‐L1 mRNA and protein in mouse and human tumor cells [19, 20] . Inflammatory cytokines in the microenvironment of tumor cells are also relevant to the tumor immune escape [21] …”

Section: Introductionmentioning

confidence: 99%

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

et al. 2020

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“…61 AT-rich interactive domain 5A (ARID5A/ Arid5a) has recently been recognized to be associated with inflammatory autoimmune diseases. 62 Distinct isoforms of RBPs have been found to play specific antiviral and immune resolution functions. 63 Thus, systematical understanding of the consequences of AS and RBP regulation in the adaptive immune system and cancer immunology will give us a new view of functions of AS in cancer.…”

Section: Discussionmentioning

confidence: 99%

Alternative splicing perturbation landscape identifies RNA binding proteins as potential therapeutic targets in cancer

Li¹,

Pan²,

Chen³

et al. 2021

Molecular Therapy - Nucleic Acids

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Alternative splicing (AS) plays an important role in gene regulation, and AS perturbations are frequently observed in cancer. RNA binding protein (RBP) is one of the molecular determinants of AS, and perturbations in RBP-gene network activity are causally associated with cancer development. Here, we performed a systematic analysis to characterize the perturbations in AS events across 18 cancer types. We showed that AS alterations were prevalent in cancer and involved in cancer-related pathways. Given that the extent of AS perturbation was associated with disease severity, we proposed a computational pipeline to identify RBP regulators. Pan-cancer analysis identified a number of conserved RBP regulators, which play important roles in regulating AS of genes involved in cancer hallmark pathways. Our application analysis revealed that the expression of 68 RBP regulators helped in cancer subtyping. Specifically, we identified four subtypes of kidney cancer with differences in cancer hallmark pathway activities and prognosis. Finally, we identified the small molecules that can potentially target the RBP genes and suggested potential candidates for cancer therapy. In summary, our comprehensive AS perturbation landscape analysis identified RBPs as potential therapeutic targets in cancer and provided novel insights into the regulatory functions of RBPs in cancer.

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“…Additionally, ARID5A, MICAL1 and RAPGEF1 appeared an obvious decline in PAAD tumor tissues than adjacent normal tissues, moreover high expression of ARID5A and MICAL1 had a longer survival time. Increasing studies have emphasized on the immunological function of AT-rich interactive domaincontaining protein 5a (ARID5A), an RNA-binding protein (RBP) [46]. The synthesis and degradation of ARID5A is regulated by Toll-like receptor 4 (TLR4)-induced NF-kB and MAPK pathways [47].…”

Section: Discussionmentioning

confidence: 99%

Identification of a five-gene prognostic signature related to B cells infiltration in pancreatic adenocarcinoma

Tang

Huang

Jiang

et al. 2021

Preprint

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Background: Pancreatic adenocarcinoma (PAAD) is an extremely malignant cancer. Immunotherapy is a promising avenue for elevating survival time of PAAD patients.Methods: The RNA sequencing and clinical data of PAAD were downloaded from the TCGA database. The ssGSEA method and weighted gene co-expression network analysis were used to calculate the relative abundance of tumor-infiltrated immune cells and identified the immune cells closely related module. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis were used to construct a prognostic model. MCPcounter and EPIC were also applied to assess the immune cell components using gene expression profile.Results: The B cells closely related module was identified and five genes including ARID5A, CLEC2B, MICAL1, MZB1 and RAPGEF1 were ultimately selected to establish the prognostic signature for calculating risk scores of PAAD patients. Kaplan-Meier curves presented a worse survival in the high-risk patients (p<0.05) and the area under the Receiver operating characteristic (ROC) curve of risk score for 1-year and 3-year survival were 0.78 and 0.80 based on the training set. Also, similar results were verified in the validated and combined sets. Interestingly, low-risk group presented significantly elevated immune, stroma scores and proportion of B cells and associations between these five genes and B cells were identified by using multiple methods including ssGSEA, MCPcounter and EPIC. Conclusions: This is the first attempt to study a B cells related prognostic signature, which is instrumental in exploration of novel prognostic biomarkers in PAAD.

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Arid5a, an RNA-Binding Protein in Immune Regulation: RNA Stability, Inflammation, and Autoimmunity

Cited by 46 publications

References 79 publications

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

Alternative splicing perturbation landscape identifies RNA binding proteins as potential therapeutic targets in cancer

Identification of a five-gene prognostic signature related to B cells infiltration in pancreatic adenocarcinoma

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