An aptamer targeting shared tumor‐specific peptide antigen of MAGE‐A3 in multiple cancers

Wang, Chin-Yu; Lin, Bai-Ling; Chen, Chung-Hsuan

doi:10.1002/ijc.29826

Cited by 26 publications

(22 citation statements)

References 51 publications

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“…9, 36 Of note, MAGE-A3 and -C2 proteins are highly expressed in HCC. 37, 38, 39 However, the mechanism of action of MAGEs and TRIM28 proteins in HCC tumors is not well understood. It has been demonstrated that MAGE proteins act as regulatory molecules to enhance the activity of E3 ubiquitin ligases.…”

Section: Discussionmentioning

confidence: 99%

MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation

et al. 2017

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Hepatocellular carcinoma (HCC) is one of the leading cause of cancer death in the world. Fructose-1,6-biphosphatase (FBP1), a rate-limiting enzyme in gluconeogenesis, has been identified recently as a tumor suppressor in HCC and other cancer types. In this study, we demonstrated that the tripartite motif-containing protein 28 (TRIM28) binds directly to and promotes FBP1 for ubiquitination and degradation. MAGE-A3 and MAGE-C2, which are known to be overexpressed in HCC, can enhance TRIM28-dependent degradation of FBP1 by forming ubiquitin ligase complexes with TRIM28. We further showed that expression of TRIM28 increased glucose consumption and lactate production by promoting FBP1 degradation in HCC cells and that FBP1 is a key mediator of TRIM28-induced HCC growth in culture and in mice. Moreover, we demonstrated that FBP1 and TRIM28 protein levels inversely correlated in HCC patient specimens. Finally, we showed that the proteasome inhibitor bortezomib mitigated the Warburg effect by inhibiting FBP1 degradation in HCC. Collectively, our findings not only identify oncogenic MAGE-TRIM28 complex-mediated proteasome degradation of FBP1 as a key mechanism underlying downregulation of FBP1 proteins in HCC, but also reveal that MAGE-TRIM28-regulated reprogramming of cancer cell metabolism and HCC tumorigenesis is mediated, at least in part, through FBP1 degradation.

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Section: Discussionmentioning

confidence: 99%

MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation

et al. 2017

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“…To confirm whether the targeting ability of the aptamer is sufficient for use as a next‐generation marker molecule, the MAp used as the target aptamer with the sequence 5′‐ATC CAG AGT GAC GCA GCA AGC ACT CAA TAT TCC CTG GAC ACG GTG GCT TAG T‐3′ was selected. [ 31 ] In Figure , the MAp sequence is verified against the DNA of the remaining specific segments. The numbers No.…”

Section: Resultsmentioning

confidence: 99%

“…This “MAp” aptamer is essentially a piece of the map that leads the nanomaterials to find the location of the tumor cells. [ 31 ] Additionally, we evaluated mouse models with different modes of administration. It is expected that sample injections could be performed using intratracheal (IT), subcutaneous (SC), and intravenous (IV) injections to evaluate the response of mice to different conditions of drug administration.…”

Section: Introductionmentioning

confidence: 99%

Next‐Generation Cancer‐Specific Hybrid Theranostic Nanomaterials: MAGE‐A3 NIR Persistent Luminescence Nanoparticles Conjugated to Afatinib for In Situ Suppression of Lung Adenocarcinoma Growth and Metastasis

et al. 2020

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NSCLC) are based mainly on the stage of cancer. [1] Once lung cancer progresses to stage III, the survival rate is only 15%. This is because the tumor cells have metastasized to the mediastinal lymph nodes, or are about to expand to the adjacent esophagus, pleura, chest wall, pericardium, or aponeurosis. Lung cancer is responsible for more deaths than breast, colon, and prostate tumors combined. A current problem in the treatment of lung cancer is the inability to do specific targeting or to trace targeting drugs for effective therapy. There are few studies on a preclinical in situ lung adenocarcinoma (LUAD) model treatment. Thus, therapeutic intervention for an effective and safe LUAD diagnosis and therapy are still challenging. Developing multi-functional nanoplatforms to sense cancer and drug delivery systems are important for tumor biology applications. For example, fluorescent nanomaterials have high resolution and can track specific cancer cells in blood circulation to facilitate diagnosis. [2][3][4] Near-infrared persistent luminescence nanoparticles (NIR PLNs) have a special nonlinear radiation process, involving the absorption and retention of photons for several hours, followed by the emission of long-term luminescenceThe rate of lung cancer has gradually increased in recent years, with an average annual increase of 15%. Afatinib (AFT) plays a key role in preventing non-small cell lung carcinoma (NSCLC) growth and spread. To increase the efficiency of drug loading and NSCLC cell tracking, near infrared-persistent luminescence nanomaterials (NIR PLNs), a silica shell-assisted synthetic route for mono-dispersal, are developed and used in the nanovehicle. After optimizing their physical and chemical properties, the NIR PLNs are able to absorb light energy and emit NIR luminescence for several hours. In this research, NIR PLNs are functionalized for drug-carrying capabilities. Effective accumulation of target drugs, such as AFT, using PLN nanomaterials can lead to unique anticancer therapeutic benefits (AFT-PLN). To minimize side effects and increase drug accumulation, nanomaterials with targeting abilities are used instead of simple drugs to inhibit the growth of tumor cells. Thus, the specific targeting aptamer, MAGE-A3 (MAp) is identified, and the PLN to increase its targeting ability (AFT-PLN@MAp) accordingly modified. The advancement of nanoscale techniques in the field of lung cancer is urgently needed; this research presents a plausible diagnostic strategy and a novel method for therapeutic administration.

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“…MAGE-A3 is one of the most frequently and highly expressed CTAs in tumors, including in 74% of metastatic melanomas, 57% of esophageal carcinomas, 39% of non-small cell lung cancers, and 38% of gastric carcinomas (30). As the expression of MAGE-A3 has been associated with malignancy and poor prognosis, it is considered a significant target for therapeutic development.…”

Section: Functionalizing Aptamers For Targeted Deliverymentioning

confidence: 99%

“…For the potential use in therapeutics, a DNA aptamer is isolated against a MAGE-A3 111–125 peptide using peptide-SELEX. The isolated MAGE-A3 aptamer shows cancer-specific binding to various cancer cells such as MCF-7 (breast cancer), SK-MEL-28 (melanoma), Cal-27 (oral cancer), DLD-1 (colorectal cancer), HepG2 (liver cancer), A-549 (lung cancer), and AsPC-1 (pancreatic cancer), but does not bind in non-tumoral cells (30). Although the authors does not perform any functional assays of MAGE-A3 aptamer activity, it has great potential for as a targeting agent to deliver therapeutics.…”

Section: Functionalizing Aptamers For Targeted Deliverymentioning

confidence: 99%

Emerging cancer-specific therapeutic aptamers

Yoon¹,

Rossi

2017

Current Opinion in Oncology

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Purpose of review We will describe recently discovered smart aptamers with tumor specificity, with an emphasis on targeted delivery of novel therapeutic molecules, cancer-specific biomarkers, and immunotherapy. Recent findings The development of cancer-specific aptamers has facilitated targeted delivery of potent therapeutic molecules to cancer cells without harming non-tumoral cells. This specificity also makes it possible to discover novel cancer biomarkers. Furthermore, alternative immune-checkpoint blockade aptamers have been developed for combinational immunotherapy. Summary Aptamers selected against cancer cells show cancer specificity, which has great potential for targeting. First, functionalizing targeted aptamers with therapeutic molecule payloads (e.g., small activating RNAs (saRNAs), anti-mitotic drugs, therapeutic antibodies, and peptides) facilitates successful delivery into cancer cells. This approach greatly improves the therapeutic index by minimizing side effects in non-tumoral cells. Second, cancer-specific proteins have been identified as cancer biomarkers through in vitro and in vivo selection, aptamer pull-down assays, and mass spectrometry. These newly discovered biomarkers improve therapeutic intervention and diagnostic specificity. In addition, the development of alternative immune-checkpoint blockade aptamers are suggested for use in combinational immunotherapeutic with current immune blockade regimens, to reduce the resistance and exhaustion of T cells in clinical trials.

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An aptamer targeting shared tumor‐specific peptide antigen of MAGE‐A3 in multiple cancers

Cited by 26 publications

References 51 publications

MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation

MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation

Next‐Generation Cancer‐Specific Hybrid Theranostic Nanomaterials: MAGE‐A3 NIR Persistent Luminescence Nanoparticles Conjugated to Afatinib for In Situ Suppression of Lung Adenocarcinoma Growth and Metastasis

Emerging cancer-specific therapeutic aptamers

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