Background: Docetaxel (DCT) is widely adopted in chemotherapy for colon cancer (CC). However, DCT resistance can cause chemotherapy failure in CC. MicroRNAs (miRNAs) are key regulators of DCT resistance. Among them, miR-194-3p is a key tumor suppressor, but how it regulates DCT resistance has not been reported yet. This research explored the molecular mechanism of miR-194-3p/Kallikrein Related Peptidase 10 (KLK10) axis in regulating DCT resistance in CC.
Methods: The expression and targeting relationship of miR-194-3p and KLK10 was dug through bioinformatics analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was adopted to determine miR-194-3p level in CC cells. The over-expressed miR-194-3p cell group was constructed to ascertain the impacts of dysregulated miR-194-3p on DCT resistance. Through dual-luciferase assay, the targeting relationship of miR-194-3p and KLK10 was uncovered. Subsequently, the in vitro cellular experiments were performed to investigate the impacts of miR-194-3p/KLK10 axis on DCT resistance in CC cells.
Results: We noticed that miR-194-3p was notably down-regulated in CC cells. The over-expressed miR-194-3p restored the DCT sensitivity of SW620/DCT and SW480/DCT cells. Dual-luciferase assay suggested the targeting relationship of miR-194-3p and KLK10. Besides, miR-194-3p negatively regulated KLK10 expression level. In vitro cellular experiments further exposed that miR-194-3p could down-regulate KLK10, thereby attenuating DCT resistance in CC cells.
Significance: miR-194-3p could overcome DCT resistance in CC cells through negatively regulating KLK10. This finding offers a potential therapeutic target for clinical treatment of DCT chemoresistance in CC.
Keywords: Colon cancer; Docetaxel resistance; KLK10; miR-194-3p.
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