Quercetin inhibits epithelial-to-mesenchymal transition (EMT) process and promotes apoptosis in prostate cancer via downregulating lncRNA MALAT1

Abstract

Background: Prostate cancer (PC) is one of the most common carcinomas in men worldwide. The lack of effective therapies urges the development of novel therapeutic options against PC. Quercetin (Quer) is a flavonoid compound that has been shown to effectively inhibit PC in vitro and in vivo. However, the underlying mechanisms await elucidation. Long non-coding RNA MALAT1 has been reported as an oncogenic target in multiple types of cancers, including PC. Previous data showed that quercetin promoted the apoptosis of fibroblast-like synoviocytes by upregulating MALAT1 in rheumatoid arthritis. However, we speculate that mechanisms are different in PC. Materials and Methods: Human PC cell line PC-3 and its xenograft tumor were chosen as in vitro and in vivo models for PC. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of MALAT1 in quercetin treatment against PC. Western blot was performed to measure the expression of related proteins to explore underlying molecular mechanisms. Results: We showed for the first time that MALAT1 expression was significantly downregulated in quercetin-treated PC cells in a dose-and time-dependent manner. Also, quercetin inhibited the proliferation of PC cells and the growth of xenograft tumors. Moreover, quercetin suppressed EMT process, promoted apoptosis and deactivated PI3K/Akt signaling pathway during the progression of PC. MALAT1 overexpression in PC cells resulted in the resistance against quercetin treatment. Conclusion: Our study illustrated, for the first time, that MALAT1 played an important role in quercetin treatment against PC by inhibiting EMT process and promoting apoptosis, providing a new molecular basis for the application of quercetin in PC treatment.