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IUBMB Life ; 66(9): 645-54, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25328987

ABSTRACT

MicroRNAs (miRNAs) are small noncoding RNAs that participate in a variety of biological processes, and dysregulation of miRNAs is widely associated with cancer development and progression. MiR-378 is frequently downregulated in colorectal cancer (CRC) and colorectal cell lines; however, it has high serum levels. Bioinformatics analysis further deduced that CDC40 is a potential target of miR-378, and luciferase reporter assays confirmed the direct regulation of CDC40 by miR-378. CDC40 plays a key role in cell cycle progression through G1/S and G2/M and pre-mRNA splicing. Subsequently, we determined that miR-378 inhibits cell growth and the G1/S transition in CRC cells and that these effects were CDC40-dependent. Finally, miR-378 increased cell apoptosis induced by the chemotherapeutic drug L-OHP. Our data highlight the potential application of miR-378 as a tumor suppressor for CRC therapy and overcoming chemoresistance, and it may also be a potential tumor marker for CRC prognosis.


Subject(s)
Apoptosis/physiology , Cell Cycle Checkpoints/physiology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/physiology , MicroRNAs/metabolism , Apoptosis/drug effects , Biomarkers, Tumor/blood , Blotting, Western , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Computational Biology , Flow Cytometry , Gene Expression Regulation, Neoplastic/genetics , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Kaplan-Meier Estimate , Luciferases , MicroRNAs/blood , Organoplatinum Compounds/pharmacology , Oxaliplatin , RNA Splicing Factors , RNA-Binding Proteins/metabolism , Real-Time Polymerase Chain Reaction , Tetrazolium Salts , Thiazoles
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