Molecular Recognition and In-Vitro-Targeted Inhibition of Renal Cell Carcinoma Using a DNA Aptamer

Abstract

Renal cell carcinoma (RCC) is the most common malignant tumor of the urinary system, and it has a high frequency of local invasion and distant metastasis. Although multiple advances have been made in the diagnosis and therapy of RCC, the vast majority of patients with metastatic RCC remain incurable. In this study, an aptamer named SW-4 against RCC 786-O cells was identified from a known sequence pool. The identified aptamer exhibited high binding affinity for target cells with dissociation constants in the nanomolar range. Binding analysis revealed that SW-4 only bound to RCC 786-O cells, but not HEK293T cells or human proximal tubular HK-2 cells, indicating that SW-4 has excellent binding selectivity. By sequence optimization, the 26-nt truncated SW-4b demonstrated improved binding affinity, and it was internalized into target cells via caveolae-mediated endocytosis in a temperature-dependent manner. Furthermore, fluorescence imaging confirmed that SW-4b accumulated at tumor sites in 786-O xenograft nude mice models and specifically recognized clinical RCC tissues. Meanwhile, SW-4b inhibited proliferation of 786-O cells by arresting cell cycle progression at the S phase. Taken together, these results indicate that SW-4b is a potential candidate for development into a novel tool for diagnosis and targeted therapy of RCC.

MTFR2, A Potential Biomarker for Prognosis and Immune Infiltrates, Promotes Progression of Gastric Cancer Based on Bioinformatics Analysis and Experiments

“…Notably, pathway enrichment analysis revealed that MTFR2 co-expressed genes were significantly enriched in the cell cycle. Cell proliferation depends on an orderly cell cycle process [55]. The results of our plate cloning assay confirm that MTFR2 can promote cell proliferation.…”

Advances in Screening and Development of Therapeutic Aptamers Against Cancer Cells

“…In the past few decades, many specific aptamers have been developed for tumor treatment ( Table 2 ), such as breast cancer ( Liu et al, 2017 ), colorectal adenocarcinoma ( Chen et al, 2017 ), lung cancer (2018), liver cancer ( Zhang G.Q. et al, 2019 ), prostate cancer ( Gray et al, 2018 ), leukemia ( Tan et al, 2019 ), renal cell carcinoma ( Zhang et al, 2018 ), oral cancer ( Simmons et al, 2014 ), cervical cancer ( Carvalho et al, 2019 ), bladder cancer ( Yao et al, 2020 ), stomach cancer ( Ding et al, 2015 ) and multiple myeloma ( Waldschmidt et al, 2017 ).…”

Oligonucleotide-Based Therapies for Renal Diseases

“…Using a mouse model of DN, aptamer treatment significantly attenuated the pathologic phenotype [ 56 ]. Aptamers have also been developed with high binding affinity and specificity to RCC cell lines [ 58 , 97 ], with the potential for their use in the identification and targeting of RCC. Zhang et al [ 58 ] identified an aptamer (SW-4) with selective binding to the RCC 786-O cell line that inhibited cell proliferation by cell cycle arrest.…”

“…Aptamers have also been developed with high binding affinity and specificity to RCC cell lines [ 58 , 97 ], with the potential for their use in the identification and targeting of RCC. Zhang et al [ 58 ] identified an aptamer (SW-4) with selective binding to the RCC 786-O cell line that inhibited cell proliferation by cell cycle arrest. Furthermore, the authors demonstrated that SW-4 retained targeting specificity to RCC in vivo following tail vein injection of the aptamer in a 786-O xenograft mouse model, and also maintained recognition of clinical RCC tissue samples.…”