Let-7a could serve as a biomarker for chemoresistance against docetaxel in gastric cancer.

BACKGROUND: MicroRNAs are noncoding RNAs which play critical roles in response to anti-cancer agents. Let-7a and miR-21 are well-known tumor-suppressor and oncomiR miRNAs, respectively. They are involved in tumorigenesis of gastric cancer and have potential to be used as markers for response to the therapy.

OBJECTIVE: We aimed to study alterations in the expression of let-7a and miR-21 and their targets in gastric cancer cell lines after treatment with docetaxel.

METHODS: GC cell lines were cultured and MTT assay was conducted to determine IC50 of docetaxel. After RNA extraction and cDNA synthesis, the expression level of miR-21 and let-7a and their targets, PDCD4 and HMGA2, were determined by quantitative real-time PCR for both treated and untreated cell lines.

RESULTS: Statistical analysis showed that the expression level of let-7a was significantly increased after treatment in AGS (p =0.004) and MKN45 (p = 0.001), while decreased in KATO III (p =0.01). On the other hand, expression level of miR-21 in treated AGS (p <0.0001), MKN45 (p= 0.006) and KATO III (p =0.01) was increased significantly. Altered expression of HMGA2 and PDCD4 genes showed different pattern in KATO III in comparison with AGS and MKN45.

CONCLUSION: Alterations in the expression level of let-7a, but not miR-21, and also its target, HMGA2, showed consistent results regarding to the more resistance of KATO III cell line with the highest IC50 concentration. Let-7a could be a novel marker for drug resistance in gastric cancer.