Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL

Iaboni, Margherita; Russo, Valentina; Fontanella, Raffaela; Roscigno, Giuseppina; Fiore, Danilo; Donnarumma, Elvira; Esposito, Carla Lucia; Quintavalle, Cristina; Giangrande, Paloma H.; Franciscis, Vittorio de; Condorelli, Gerolama

doi:10.1038/mtna.2016.5

Cited by 61 publications

(49 citation statements)

References 57 publications

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“…More importantly, following axl-148b conjugate administration into mouse xenotransplants, increased tumor necrosis and apoptosis were observed in the primary masses, together with a strong reduction of CTCs and metastasis formation in distant organs. The chimeric axl-148b molecule used in our investigation resulted highly specific for AXL + cells, similarly to what observed here or previously for GL21.T [18][19][20]25]. In fact, treatments with axl-148b conjugate allowed an efficient increase of miR-148b in AXL + but not in AXLcells.…”

Section: Discussionsupporting

confidence: 85%

“…However, apart from acting on their targets, aptamers can be used as carriers to convey therapeutic tools (chemotherapy drugs, siRNAs and miRNAs) to cells in a specific manner [13][14][15][16][17]. Since most tumor cells overexpress AXL, a tyrosine kinase receptor with oncogenic functions, an RNA aptamer against AXL, GL21.T, has been developed and used to block AXL downstream signaling [18] and to selectively deliver small non-coding RNAs [19][20][21]. In our work, we conjugated miR-148b to GL21.T to generate an axl-miR-148b conjugate or chimeric aptamer (from now on, briefly called axl-148b), and obtained a specific increase of miR-148b in treated AXL-expressing cells with the consequent silencing of ALCAM and ITGA5, two miR-148b direct targets.…”

Section: Ivyspringmentioning

confidence: 99%

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Axl-148b chimeric aptamers inhibit breast cancer and melanoma progression

Quirico¹,

Orso²,

Esposito³

et al. 2020

Int. J. Biol. Sci.

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microRNAs (miRNAs) are small non-coding RNAs acting as negative regulators of gene expression and involved in tumor progression. We recently showed that inhibition of the pro-metastatic miR-214 and simultaneous overexpression of its downstream player, the anti-metastatic miR-148b, strongly reduced metastasis formation. To explore the therapeutic potential of miR-148b, we generated a conjugated molecule aimed to target miR-148b expression selectively to tumor cells. Precisely, we linked miR-148b to GL21.T, an aptamer able to specifically bind to AXL, an oncogenic tyrosine kinase receptor highly expressed on cancer cells. Axl-148b conjugate was able to inhibit migration and invasion of AXL-positive, but not AXL-negative, cancer cells, demonstrating high efficacy and selectivity in vitro. In parallel, expression of ALCAM and ITGA5, two miR-148b direct targets, was reduced. More importantly, axl-148b chimeric aptamers were able to inhibit formation and growth of 3D-mammospheres, to induce necrosis and apoptosis of treated xenotransplants, as well as to block breast cancer and melanoma dissemination and metastatization in mice. Relevantly, axl aptamer acted as specific delivery tool for miR-148b, but it also actively contributed to inhibit metastasis formation, together with miR-148b. In conclusion, our data show that axl-148b conjugate is able to inhibit tumor progression in an axl-and miR-148b-dependent manner, suggesting its potential development as therapeutic molecule.

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Section: Discussionsupporting

confidence: 85%

Section: Ivyspringmentioning

confidence: 99%

Axl-148b chimeric aptamers inhibit breast cancer and melanoma progression

Quirico¹,

Orso²,

Esposito³

et al. 2020

Int. J. Biol. Sci.

Self Cite

View full text Add to dashboard Cite

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“…Recent evidence showed that the technique of targeted gene expression, including specific gene-promoter-operating expression and distinct delivery systems, is a crucial strategy for gene therapy against various cancers including lung cancer 4, 5, 6, 7. And, microRNAs (miRNAs), which are endogenous 21- to 23-nt non-coding RNAs, have pointed to central regulatory roles in the development of lung cancer and emerged as important targets for gene therapy against clinical lung cancer 8, 9, 10, 11. This research suggested that targeted expression of distinct miRNA molecules might be a useful therapeutic strategy for lung cancer, which would be ultimately benefit to the outcome of clinical lung cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Targeted Expression of miR-7 Operated by TTF-1 Promoter Inhibited the Growth of Human Lung Cancer through the NDUFA4 Pathway

Chen

Zhao

et al. 2017

Molecular Therapy - Nucleic Acids

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Targeted expression of gene technique is an important therapeutic strategy for lung cancer. MicroRNA-7 has been well documented as a promising tumor suppressor but never been test in specific gene-promoter-targeted expression in cancer gene therapy. Here, we first evaluated the efficacy of miR-7 expression operated by the promoter of TTF-1, a lineage-specific oncogene in lung cancer, in vitro using an eukaryotic vector of TTF-1-promoter-operated expression of miR-7 (termed as p-T-miR-7). Interestingly, using a nude mice model, the growth and metastasis of human lung cancer cells in vivo were significantly reduced in remote hypodermic injection of the p-T-miR-7 group, accompanied by increased expression of miR-7 and reduced transduction of the Akt and Erk pathway in situ. Mechanism aspect, global gene expression analysis showed that downregulation of NDUFA4, a novel target of miR-7, contributed to the effects of miR-7 expression operated by TTF-1 promoter on the growth and metastasis of human lung cancer cells, as well as altered transduction of the Akt and Erk pathway. Finally, there was no significant difference in weight or histopathology of other organs. These data provided a basis for development of novel modality of miRNA-based targeted expression therapy against clinical lung cancer.

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“…Aptamers are suitable for targeting as they are noncytotoxic, non‐immunogenic, with superior tissue penetration, easy to modify and cheap . Conjugation of miRNAs to aptamers has been used to specifically target the nucleic acid to cells expressing the ligands recognized by the aptamer . Conjugation to cell‐penetrating peptides enables crossing of cell and endosomal membranes.…”

Section: The Utility Of Mirnas As New Therapeutic Targetsmentioning

confidence: 99%

MicroRNA as novel biomarkers and therapeutic targets in diabetic kidney disease: An update

et al. 2019

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Diabetic kidney disease (DKD) is a life‐limiting condition characterized by progressive and irreversible loss of renal function. Currently, the estimated glomerular filtration rate (eGFR) and albuminuria are used as key markers to define DKD. However, they may not accurately indicate the degree of renal dysfunction and injury. Current therapeutic approaches for DKD, including attainment of blood pressure goals, optimal control of blood glucose and lipid levels, and the use of agents to block the renin‐angiotensin‐aldosterone system (RAAS) can only slow the progression of DKD. Hence, early diagnosis and innovative strategies are needed to both prevent and treat DKD. In recent years, a novel class of noncoding RNA, microRNAs (miRNAs) are reported to be involved in all biological processes, including cellular proliferation, apoptosis, and differentiation. miRNAs are small noncoding RNAs that regulate gene expression by posttranscriptional and epigenetic mechanisms. They are found to be in virtually all body fluids and used successfully as biomarkers for various diseases. Urinary miRNAs correlate with clinical and histologic parameters in DKD and differential urinary miRNA expression patterns have been reported. Kidney fibrosis is the common end stage of various CKD including DKD. Transforming growth factor‐β(TGF‐β) is regarded as the master regulator of kidney fibrosis, which is likely at least in part through regulating miRNA expression. miRNA are widely involved in the progression of DKD via many molecular mechanisms. In this review, the involvement of miRNA in fibrosis, inflammation, hypertrophy, autophagy, endoplasmic reticulum (ER) stress, oxidative stress, insulin resistance, and podocyte injury will be discussed, as these mechanisms are believed to offer new therapeutic targets that can be exploited to develop important treatments for DKD over the next decade.

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Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL

Cited by 61 publications

References 57 publications

Axl-148b chimeric aptamers inhibit breast cancer and melanoma progression

Axl-148b chimeric aptamers inhibit breast cancer and melanoma progression

Targeted Expression of miR-7 Operated by TTF-1 Promoter Inhibited the Growth of Human Lung Cancer through the NDUFA4 Pathway

MicroRNA as novel biomarkers and therapeutic targets in diabetic kidney disease: An update

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