G‐quadruplex‐enhanced circular single‐stranded DNA (G4‐CSSD) adsorption of miRNA to inhibit colon cancer progression

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 8; pp. 9774 - 9787
• Main Authors: Wu, Haidong, Zhong, Weilong, Zhang, Ronghua, Ding, Yuping, Qu, Chunhua, Lai, Keguan, Pang, Zheng, Yin, Shan, Zhang, Guangling, Chen, Shuang
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.04.2023; John Wiley and Sons Inc; Wiley
• Subjects: Adsorption; Cancer therapies; Cell proliferation; Cells; Chemotherapy; Chloride channels (calcium-gated); circular single‐stranded DNA; Cloning; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - therapy; Colorectal cancer; DNA; DNA structure; DNA, Single-Stranded - genetics; Drug delivery; Drug development; Drug resistance; G quadruplex; G-Quadruplexes; Gene Expression Regulation, Neoplastic; Genomes; Glucuronosyltransferase; Humans; Immunotherapy; Metastases; Metastasis; microRNA inhibitor; MicroRNAs - genetics; miRNA; Mutation; N-Acetylglucosinyldiphosphodolichol N-acetylglucosaminyltransferase; Polyclonal antibodies; Protein structure; Proteins; Secondary structure; Single-stranded DNA; Tumor suppressor genes; Tumors; tumour suppressor gene; Beijing China; United States > US; China; Japan; tumour suppressor gene; G quadruplex; circular single-stranded DNA; microRNA inhibitor; colon cancer
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.5721

Background Chromosomal heterogeneity leads to the abnormal expression and mutation of tumor‐specific genes. Drugs targeting oncogenes have been extensively developed. However, given the random mutation of tumor suppressor genes, the development of its targeted drugs is difficult. Methods Our early research revealed that artificial circular single‐stranded DNA (CSSD) can restore multiple tumor suppressor genes to inhibit tumor malignant progression by adsorbing miRNA. Here, we improved CSSD to a fully closed single‐stranded DNA with G quadruplex DNA secondary structure (G4‐CSSD), which made G4‐CSSD with higher acquisition rate and decreased degradation. The Cancer Genome Atlas (TCGA) and Human Protein Atlas database were used to predict tumour suppressor genes in colon cancer. Cellular and animal experiments were performed to validate the role of G4‐CSSD in cancer cell progression. Results In colon cancer, we observed the simultaneous low expressions of chloride channel accessory 1 (CLCA1), UDP‐GlcNAc:betaGal beta‐1,3‐N‐acetylglucosaminyltransferase 6 (B3GNT6) and UDP glucuronosyltransferase family 2 member A3 (UGT2A3), which indicated an favourable prognosis. After repressing miR‐590‐3p with G4‐CSSD590, the upregulation of CLCA1, B3GNT6 and UGT2A3 inhibited the proliferation and metastasis of colon cancer cells. Conclusions This study may provide basis for new treatment methods for colon cancer by restoration of tumor suppressor genes. G4‐CSSD restorestumor suppressor genes expression to inhibit tumor progression. CSSD with G quadruplex (G4) adsorbs microRNA like a magnet, thus releasing tumor suppressor genes and restoring their expression. So as to inhibit the progression of malignant tumor.