title: Seed-targeting anti-miR-21 inhibiting malignant progression of retinoblastoma and analysis of their phosphorylation signaling pathways.
abstract: MiR-21 acts as a ubiquitous oncogene in major classes of human cancers and is a potential target for therapeutic intervention. However, the relative expression of miR-21 in retinoblastoma is poorly understood. Here we detected miR-21 expression in HXO-RB44 cell line human normal retinal tissues and retinoblastoma (Rb) tissue specimens, and studied its function using an 8-mer tiny seed-targeting anti-miR-21 (t-anti-miR-21). RT-PCR revealed that miR-21 was highly overexpressed in HXO-RB44 cells and Rb tissue specimens compared with normal human retinal tissues. The localization and transfection efficiency of t-anti-miR-21 and the cell cycle distribution were detected by confocal microscopy and flow cytometry. In addition, we found that t-anti-miR-21 led to a significant inhibition of retinoblastoma cell proliferation, migration and colony formation in vitro, with a similar effect to anti-miR-21. Anti-miR-21 down-regulated the miR-21 level, whereas both 8-mer t-anti-miR-21 and 15-mer m-anti-miR-21 had no impact on miR-21 expression levels. Finally, the phosphorylation signaling pathway, down-regulated by t-anti-miR-21, was integrated by KEGG assay, which elucidated the potential mechanisms of inhibition of miR-21 in retinoblastoma. Taken together, knockdown of miR-21 in the HXO-RB44 cell is capable of inhibiting cancer progression in retinoblastoma. Seed-targeting t-anti-miR-21 was a novel strategy for mir-21-based therapeutics and drug discovery.
authors.affiliation: Department of Ophthalmology, Affiliated First Hospital of Jinan University, Guangzhou 510632, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Ophthalmology, Affiliated First Hospital of Jinan University, Guangzhou 510632, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Affiliated First Hospital of Jinan University, Guangzhou 510632, China.
authors.forename: Junzhong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Human Parasitology, Medical College of Jinan University, Guangzhou 510632, China.
authors.forename: Chunyun
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Affiliated First Hospital of Jinan University, Guangzhou 510632, China.
authors.forename: Ruojing
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Jinan University, 601 Western Huangpu Avenue, Guangzhou 510632, China.
authors.forename: Rongxuan
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Jinan University, 601 Western Huangpu Avenue, Guangzhou 510632, China. Electronic address: efeijia@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Fei
mesh_terms: D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018613:Microscopy, Confocal; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D010766:Phosphorylation; D040081:Protein Array Analysis; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism; D019572:Retinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense
keywords: KEGG; cell migration; colony formation; microRNA-21; phosphorylation signaling pathway; retinoblastoma; seed-targeting; tiny anti-miRNA