Corylin sensitizes breast cancer cells to overcome tamoxifen resistance by regulating OAS1/miR-22-3p/SIRT1 axis

Breast cancer (BCa) is one of the leading causes of can-cer-related death among women worldwide. At present, the clinical treatment with tamoxifen (TAM) is chal-lenged by the development of drug resistance. To in-vestigate the effect of corylin on TAM resistance in BCa cells, this study investigated the molecular mechanisms involving miRNA-mRNA targets modulated by corylin. The TAM-resistant MCF-7TR and T47DTR cell lines were generated, and it was found that corylin treatment re-duced the cell viability of these cells significantly. Fur-thermore, OAS1 was validated to be highly expressed in TAM-resistant cells, while OAS1 knockdown sensitized MCF-7TR and T47DTR cells to TAM treatment. Mean-while, OAS1 was also repressed by corylin treatment, indicating that OAS1 was a key regulator of corylin func-tion. Through bioinformatic analysis, the tumor suppres-sive miRNA miR-22-3p was identified to directly target and inhibit OAS1. Moreover, corylin treatment up-regu-lated miR-22-3p expression, which thus down-regulated the OAS1 expression. Interestingly, OAS1 itself func-tioned as a miR-22-3p sponge to repress miR-22-3p ex-pression. Further, SIRT1 was identified to be up-regulat-ed in TAM-resistant cells and participated in the OAS1/ miR-22-3p regulatory axis via the miR-22-3p direct tar-get. In conclusion, corylin sensitized TAM-resistant cells to TAM treatment by inhibiting OAS1 expression and modulating the OAS1/miR-22-3p/SIRT1 axis.