Alternative splicing of TIA‐1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance

Zadeh, M.A. Hamdollah; Amin, Elianna; Hoareau-Aveilla, Coralie; Domingo, Enric; Symonds, Kirsty E.; Yang, Xi; Heesom, Katherine J.; D'Silva, Olivia; Betteridge, Kai; Williams, Ann C.; Kerr, David; Salmon, Andrew; Oltean, Sebastian; Midgley, Rachel; Ladomery, Michael; Harper, Steven J.; Varey, Alexander H. R.; Bates, David O.

doi:10.1016/j.molonc.2014.07.017

Cited by 64 publications

(58 citation statements)

References 30 publications

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“…The intracellular RNA binding protein T‐cell Intracellular Antigen‐1 ( TIA‐1 ) controls VEGFA isoform expression. A recent investigation identified KRAS ‐dependent splicing of TIA‐1 as a mechanism of resistance to angiogenesis targeting therapies, thus adding an additional layer of complexity to colorectal cancer angiogenesis (Hamdollah Zadeh et al, ). However, the exact mechanism by which KRAS mediates TIA‐1 splicing remains unknown.…”

Section: Mirnas and Resistance To Bevacizumabmentioning

confidence: 99%

MicroRNAs in cancer drug resistance: Basic evidence and clinical applications

Ghasabi

Mansoori

Mohammadi

et al. 2018

Journal Cellular Physiology

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Development of drug resistance has considerably limited the efficacy of cancer treatments, including chemotherapy and targeted therapies. Hence, understanding the molecular mechanisms underpinning the innate or the acquired resistance to these therapies is critical to improve drug efficiency and clinical outcomes. Several studies have implicated microRNAs (miRNA) in this process. MiRNAs repress gene expression by specific binding to complementary sequences in the 3' region of target messenger RNAs (mRNAs), followed by target mRNA degradation or blocked translation. By targeting molecules specific to a particular pathway within tumor cells, the new generation of cancer treatment strategies has shown significant advantages over conventional chemotherapy. However, the long-term efficacy of targeted therapies often remains poor, because tumor cells develop resistance to such therapeutics. Targeted therapies often involve monoclonal antibodies (mAbs), such as those blocking the ErB/HER tyrosine kinases, epidermal growth factor receptor (cetuximab) and HER2 (trastuzumab), and those inhibiting vascular endothelial growth factor receptor signaling (e.g., bevacizumab). Even though these are among the most used agents in tumor medicine, clinical response to these drugs is reduced due to the emergence of drug resistance as a result of toxic effects in the tumor microenvironment. Research on different types of human cancers has revealed that aberrant expression of miRNAs promotes resistance to the aforementioned drugs. In this study, we review the mechanisms of tumor cell resistance to mAb therapies and the role of miRNAs therein. Emerging treatment strategies combine therapies using innovative miRNA mimics or antagonizers with conventional approaches to maximize outcomes of patients with cancer.

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Section: Mirnas and Resistance To Bevacizumabmentioning

confidence: 99%

MicroRNAs in cancer drug resistance: Basic evidence and clinical applications

Ghasabi

Mansoori

Mohammadi

et al. 2018

Journal Cellular Physiology

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“…The splice variants are differentially regulated (e.g., SRPK1 stimulates splicing to VEGFA 165 a, and Clk1/4 stimulates splicing to VEGFA 165 b) (Nowak et al 2008(Nowak et al , 2010 and are differentially regulated post-transcriptionally -for example, by T-cell intracellular antigen-1, an RNA-binding protein that differentially regulates translation and splicing of VEGF through activation by Ras (Hamdollah Zadeh et al 2015).…”

Section: Transcriptional Regulation Of Pro-angiogenesis Pathways In Pcamentioning

confidence: 99%

Regulation of vascular endothelial growth factor in prostate cancer

Brot¹,

Ntekim²,

Cardenas³

et al. 2015

Endocrine-Related Cancer

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Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to w30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically %24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling.

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“…In this model, IL‐10 directly suppressed proinflammatory cytokines by down‐regulating HuR as a result of ventricular dysfunction by injury. TTP, TIA‐1 and TIAR have also been reported to regulate some diseases, including inflammation, fibrosis, angiogenesis, cell death and proliferation, similar to HuR . The imbalance in HuR/TTP alters the differential mRNA expression of the inflammatory cytokines, granulocyte–macrophage colony‐stimulating factor (GM‐CSF), IL‐6, IL‐8, TNF‐α and IL‐10 in eutopic and ectopic endometriosis from that in healthy donors .…”

Section: Discussionmentioning

confidence: 99%

The induced RNA-binding protein, HuR, targets 3′-UTR region of IL-6 mRNA and enhances its stabilization in periodontitis

Ouhara

Munenaga

Kajiya

et al. 2018

Clinical and Experimental Immunology

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RNA-binding proteins (RBPs) regulate mRNA stability by binding to the 3'-untranslated region (UTR) region of mRNA. Human antigen-R (HuR), one of the RBPs, is involved in the progression of diseases, such as rheumatoid arthritis, diabetes mellitus and some inflammatory diseases. Interleukin (IL)-6 is a major inflammatory cytokine regulated by HuR binding to mRNA. Periodontal disease (PD) is also an inflammatory disease caused by elevations in IL-6 following an infection by periodontopathogenic bacteria. The involvement of HuR in the progression of PD was assessed using in-vitro and in-vivo experiments. Immunohistochemistry of inflamed periodontal tissue showed strong staining of HuR in the epithelium and connective tissue. HuR mRNA and protein level was increased following stimulation with Porphyromonas gingivalis (Pg), one of the periodontopathogenic bacteria, lipopolysacchride (LPS)-derived from Pg (PgLPS) and tumour necrosis factor (TNF)-α in OBA-9, an immortalized human gingival epithelial cell. The luciferase activity of 3'-UTR of IL-6 mRNA was increased by TNF-α, Pg and PgLPS in OBA-9. Luciferase activity was also increased in HuR-over-expressing OBA-9 following a bacterial stimulation. Down-regulation of HuR by siRNA resulted in a decrease in mRNA expression and production of IL-6. In contrast, the over-expression of HuR increased IL-6 mRNA expression and production in OBA-9. The HuR inhibitor, quercetin, suppressed Pg-induced HuR mRNA expression and IL-6 production in OBA-9. An oral inoculation with quercetin also inhibited bone resorption in ligature-induced periodontitis model mice as a result of down-regulation of IL-6. These results show that HuR modulates inflammatory responses by regulating IL-6.

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Alternative splicing of TIA‐1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance

Cited by 64 publications

References 30 publications

MicroRNAs in cancer drug resistance: Basic evidence and clinical applications

MicroRNAs in cancer drug resistance: Basic evidence and clinical applications

Regulation of vascular endothelial growth factor in prostate cancer

The induced RNA-binding protein, HuR, targets 3′-UTR region of IL-6 mRNA and enhances its stabilization in periodontitis

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