MiR-223 regulates CDDP resistance in pancreatic cancer via targeting FoxO3a.

Abstract

FoxO3a is a well-defined tumor suppressor gene in the forkhead transcription factor O subfamily (FoxO), and its reduction is related to the occurrence of various tumors. It was found that miR-223 expression is abnormally elevated in pancreatic cancer tissues. Bioinformatics analysis revealed a targeted complementary binding relationship between miR-223 and FoxO3a. This study explored whether miR-155 regulates the expression of FoxO3a and affects the proliferation, apoptosis, and cisplatin (CDDP) resistance of oral cancer cells. Dual-Luciferase reporter gene assay validated the targeted relationship between miR-223 and FoxO3a. The CDDP-resistant pancreatic cancer cell line BXPC3/CDDP was established, and the expressions of miR-223 and FoxO3a were compared. BXPC3/CDDP cells were divided into miR-NC group and miR-223 inhibitor group. QRT-PCR was adopted to test miR-223 and FoxO3a mRNA expressions. Western blot was performed to determine FoxO3a protein expression. Cell apoptosis was detected by flow cytometry and cell proliferation was detected by EdU staining. There was a targeted regulatory relationship between miR-223 and FoxO3a mRNA. The expression of miR-223 was significantly higher, while the expression of FoxO3a mRNA and protein was significantly lower in BXPC3/CDDP cells than that in BXPC3 cells. Cell Counting Kit-8 (CCK-8) experiments showed that the same concentration of CDDP exhibited significantly lower proliferation inhibition in BXPC3/CDDP cells than BXPC3 cells. Compared with miR-NC group, transfection of miR-223 inhibitor significantly increased the expression of FoxO3a in BXPC3/CDDP cells, which significantly attenuated cell proliferation and enhanced apoptosis in CDDP-treated cells. Increased expression of miR-233 was associated with CDDP resistance in pancreatic cancer cells. Inhibition of miR-223 expression upregulated FoxO3a expression, restrained pancreatic cancer cell proliferation, promoted cell apoptosis, and enhanced CDDP sensitivity in pancreatic cancer cells.