Hsa-miRNA-765 as a Key Mediator for Inhibiting Growth, Migration and Invasion in Fulvestrant-Treated Prostate Cancer

Abstract

Fulvestrant (ICI-182,780) has recently been shown to effectively suppress prostate cancer cell growth in vitro and in vivo. But it is unclear whether microRNAs play a role in regulating oncogene expression in fulvestrant-treated prostate cancer. Here, this study reports hsa-miR-765 as the first fulvestrant-driven, ERβ-regulated miRNA exhibiting significant tumor suppressor activities like fulvestrant, against prostate cancer cell growth via blockage of cell-cycle progression at the G2/M transition, and cell migration and invasion possibly via reduction of filopodia/intense stress-fiber formation. Fulvestrant was shown to upregulate hsa-miR-765 expression through recruitment of ERβ to the 5′-regulatory-region of hsa-miR-765. HMGA1, an oncogenic protein in prostate cancer, was identified as a downstream target of hsa-miR-765 and fulvestrant in cell-based experiments and a clinical study. Both the antiestrogen and the hsa-miR-765 mimic suppressed HMGA1 protein expression. In a neo-adjuvant study, levels of hsa-miR-765 were increased and HMGA1 expression was almost completely lost in prostate cancer specimens from patients treated with a single dose (250 mg) of fulvestrant 28 days before prostatectomy. These findings reveal a novel fulvestrant signaling cascade involving ERβ-mediated transcriptional upregulation of hsa-miR-765 that suppresses HMGA1 protein expression as part of the mechanism underlying the tumor suppressor action of fulvestrant in prostate cancer.

Inhibition of S-Adenosylmethionine-Dependent Methyltransferase Attenuates TGFβ1-Induced EMT and Metastasis in Pancreatic Cancer: Putative Roles of miR-663a and miR-4787-5p

“…For instance, DZNep induced the expressions of ~50 miRNAs by ≥1.5–10 folds. Of these miRs, several candidates have been reported earlier to confer anti-tumorigenic roles in various solid tumors (35–41). While they provide supportive evidence for DZNep’s growth control effects in PDAC, comparison of DZNep-induced miRNAs with downregulated miRNA datasets in PDAC further revealed which miRNAs are playing a role in the TGF-β1-induced EMT.…”

MicroRNA-765 Enhances the Anti-Angiogenic Effect of CDDP via APE1 in Osteosarcoma

“…There are currently reported in the literature that cisplatin-induced resistance is mediated by miR-21-3p in ovarian cells 13 , and miRNA-21 increases cisplatin sensitivity of osteosarcoma by repressing the expression of Sprouty2 14 . In addition, miR-765 as a regulatory point in the treatment of prostate cancer patients after treatment of fulvestrant, the impact of prostate cancer generation, migration and invasive ability 15 . However, there is a litter study regarding the association between anti-angiogenic effect of cisplatin and miR-765.…”

Role of microRNA-30c Targeting ADAM19 in Colorectal Cancer

“…MiRNAs are dysregulated in a variety of cancers and miRNAs play an important role in tumorigenesis [ 2 , 3 , 4 , 5 ]. A number of miRNAs have been found to act as tumor suppressors [ 2 , 6 , 7 , 8 ]. In recent years, miRNAs have been recognized as critical regulators in development and progression of cancer including colorectal cancer (CRC) [ 9 , 10 , 11 , 12 ].…”