In Vivo Selection Against Human Colorectal Cancer Xenografts Identifies an Aptamer That Targets RNA Helicase Protein DHX9

Mi, Jing; Ray, Partha Pratim; Liu, Jenny; Kuan, Chien-Tsun; Xu, Jennifer; Hsu, David S.; Sullenger, Bruce A.; White, Rebekah R.; Clary, Bryan M.

doi:10.1038/mtna.2016.27

Cited by 52 publications

(49 citation statements)

References 23 publications

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“…[43]. DHX9 is closely related to the development of various cancers, such as breast cancer [44], colon cancer [45], lung cancer [40], liver cancer [46], Ewing sarcoma [47], and so on. DHX9 can bind to the inverted complementary ALU sequences which lie in the flank of circRNAs to reduce the formation of circRNAs [19].…”

Section: Discussionmentioning

confidence: 99%

Hsa_Circ_0001206 is downregulated and inhibits cell proliferation, migration and invasion in prostate cancer

Song

Zhuo

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Our study is to explore the expression profiles and potential functions of circRNAs in prostate cancer (PCa). A total of 95 circRNAs and 830 mRNAs were screened to be significantly differentially expressed in PCa tissues by microarrays. Co-expression and competitive endogenous RNA (ceRNA) network were constructed to reveal the potential regulatory mechanisms of circRNAs. Three circRNAs, hsa_circ_0001206, hsa_circ_0001633, and hsa_circ_0009061 were validated to be down-regulated in PCa by quantitative real-time PCR (qRT-PCR) and hsa_circ_0001206 as well as hsa_circ_0009061 was significantly associated with clinical features of PCa patients. Meanwhile, Receiver Operating Characteristic (ROC) curves showed their good diagnostic value as biomarkers for PCa. The down-regulation of hsa_circ_001206 was partly because of the regulation of DExH-Box Helicase 9 (DHX9). Moreover, overexpression of hsa_circ_0001206 inhibited PCa cell proliferation, migration, and invasion in vitro and prevented tumor growth in vivo. Dual-luciferase reporter assays showed hsa_circ_0001206 could directly bind to miR-1285-5p. The expression of Smad4, a well-known suppressive gene in PCa, can be increased by overexpression of hsa_circ_0001206 and this effect could be partly reversed by co-transfection of miR-1285-5p mimic. The study revealed expression profiles and potential functions of circRNAs and demonstrated hsa_circ_0001206 played a suppressive role in the pathogenesis of PCa. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Hsa_Circ_0001206 is downregulated and inhibits cell proliferation, migration and invasion in prostate cancer

Song

Zhuo

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…DExH-Box Helicase 9 (DHX9) is a member of the DEAH-containing family of RNA helicases which has the ability to bind RNAs and catalyze the ATP-dependent unwinding of double-stranded RNAs (dsRNAs) [35]. It has been reported it is dysregulated in multiple human cancers [20], [21]. In this study, we found that the overexpression of SNORA42 suppressed the degradation of DHX9 and ubiquitination of DHX9, whereas had no effects on DHX9 mRNA level, indicating that SNORA42 promotes DHX9 expression by inhibiting its degradation, not the generation.…”

Section: Discussionmentioning

confidence: 99%

SNORA42 Promote Oesophageal Squamous Cell Carcinoma Development Through Interacting With Dhx9

Shan

Wei

Xiang

et al. 2020

Preprint

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Background:Oesophageal squamous cell carcinoma (ESCC) is a high malignant cancer, which is the most common subtype of oesophageal cancer. Small nucleolar RNAs (snoRNAs) are a group of novel non-coding RNAs that have been found play a key role in various cancers. Methods:The expression of SNORA42 in ESCC samples and cell lines was measured by using real-time PCR and a series of in vitro and in vivo assays were performed to determine the function of SNORA42 in ESCC. Furthermore, RNA pull-down assay combined with Mass Spectrometry was applied to identify the protein that is associated with SNORA42. Silencing SNORA42 in ESCC cell followed by Next-Generation mRNA Sequencing was used to investigate the signaling pathway regulated by SNORA42.Results: We identified H/ACA box snoRNA42 (SNORA42) wasupregulated in ESCC and had the potential to be applied as a prognostic marker. Specifically, overexpression of SNORA42 promotedESCCprogressionin vitro and in vivo, whereas knockdown of SNORA42 had opposite effects. We identified SNORA42 interacted with DHX9, which was up-regulated in ESCC and had a positive correlation with the expression of SNORA42. Furthermore, the promotion of SNORA42 on ESCC phenotypes can be reversed by knockdown of DHX9. Mechanically, SNORA42 promoted DHX9 expression by attenuating DHX9 transports into cytoplasm, to protect DHX9 from being ubiquitinated and degraded. From KEGG analysis of Next-Generation Sequencing, the NF-κB pathway was one of the most regulated pathways by SNORA42. SNORA42 enhanced phosphorylation of p65 and this effect could be reversed by NF-κB inhibitor, BAY11-7082. Moreover, SNORA42 activated NF-κB signaling through promotingthe transcriptional co-activator DHX9 interacted with p-p65, inducingNF-κB downstream genes expression. Conclusions:These findings suggest that SNORA42 is up-regulated in ESCC and promotes ESCC developments,partly via interacting with DHX9 and triggering SNORA42/DHX9/p65 axis.

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“…In vivo SELEX is a direct and reliable technique for the identification of aptamers that selectively recognize diseased organs or tissues in animal models. 17 Using selected aptamers, we can develop targeting moiety-equipped nano-based delivery systems with high efficiency and specificity to overcome particularly robust biological barrier, such as bone and brain, and realize targeted drug delivery. The tumor endothelial cell-based active targeting strategy developed in this study can deliver therapeutics to tumor adjacent area to kill cancer cells and has great value in targeting tumor endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

In vivo SELEX of bone targeting aptamer in prostate cancer bone metastasis model

Chen

Jiang

et al. 2018

IJN

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PurposePB is one of the most severe complications of late stage prostate cancer and negatively impacts patient quality of life. A major challenge for the treatment of cancer bone metastasis is the management of efficient drug delivery to metastatic bone lesion. We aimed to explore the use of aptamers as promising tools to develop a targeted drug delivery system for PBs.Materials and methodsIn vivo SELEX was applied to identify bone targeting aptamer in a mouse model with PBs.ResultsThe aptamer (designated as “PB”) with the highest bone targeting frequency in mice bearing PC3 PB was selected for further analysis. The PB aptamer specifically targeted modulated endothelial cells in response to cancer cells in the bones of mice bearing PC3 PBs. The targeting efficiency of the PB aptamer conjugated to gold particles was verified in vivo.ConclusionThis investigation highlights the promise of in vivo SELEX for the discovery of bone targeting aptamers for use in drug delivery.

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In Vivo Selection Against Human Colorectal Cancer Xenografts Identifies an Aptamer That Targets RNA Helicase Protein DHX9

Cited by 52 publications

References 23 publications

Hsa_Circ_0001206 is downregulated and inhibits cell proliferation, migration and invasion in prostate cancer

Hsa_Circ_0001206 is downregulated and inhibits cell proliferation, migration and invasion in prostate cancer

SNORA42 Promote Oesophageal Squamous Cell Carcinoma Development Through Interacting With Dhx9

In vivo SELEX of bone targeting aptamer in prostate cancer bone metastasis model

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