Downregulation of microRNA-574 in cancer stem cells causes recurrence of prostate cancer via targeting REL

Abstract

miR‑574‑5p has been reported involved in the pathogenesis of numerous human malignancies such as colorectal and lung cancer. In this study, we aimed to explore the roles of REL and miR‑574 in the recurrence of prostate cancer (PCa) and to identify the underlying molecular mechanisms. Our literature search found that miR‑574 is regulated in cancer stem cells (CSCs), and next we used the microRNA (miRNA) database (www.mirdb.org) to find REL as a target of miR‑574. Luciferase assay was performed to verify the miRNA/target relationship. Oligo-transfection, real‑time PCR and western blot analysis were used to support the conclusions. We validated REL to be the direct gene via luciferase reporter assay system, and real‑time PCR and western blot analysis were also conducted to study the mRNA and protein expression level of REL between different groups (recurrence and non‑recurrence) or cells treated with scramble control, miR‑574 mimics, REL siRNA and miR‑574 inhibitors, indicating the negative regulatory relationship between miR‑574 and REL. We also investigated the relative viability of prostate CSCs when transfected with scramble control, miR‑574 mimics, REL siRNA and miR‑574 inhibitors to validate miR‑574 to be positively interfering with the viability of prostate CSCs. We then investigated the relative apoptosis of prostate CSCs when transfected with scramble control, miR‑574 mimics, REL siRNA and miR‑574 inhibitors. The results showed miR‑574 inhibited apoptosis. In conclusion, miR‑574 might be a novel prognostic and therapeutic target in the management of PCa recurrence.

MicroRNA Expression Profile in Peripheral Blood Lymphocytes of Sheep Vaccinated with Nigeria 75/1 Peste Des Petits Ruminants Virus

“…Previous reports showed that miR-744 and miR-574 played role in inhibition of cell proliferation and invasion or tumor-suppressive in different human malignancies, which might be novel and efficient therapeutic targets [80,81,82]. In addition, miR-574 also could inhibit apoptosis [83]. On comparing PPR vaccine virus and PPR virulent virus, the miR-30 and let-7 family were commonly differentially expressed in spleen and lung tissues of goats infected with PPR virulent virus in vivo at 10 dpi, PBMC of goat infected with PPR virulent virus in vivo at 9 dpi, PBMC of goat inoculated with PPR vaccine virus in vitro at 1 dpi, and PBMC of sheep inoculated with PPR vaccine virus in vivo .…”

Epi-miRNAs: Regulators of the Histone Modification Machinery in Human Cancer

“…Additionally, a study by Hu J. et al showed that miR-93 is a key regulator of EZH1 as well as JAK1, STAT3, AKT3, SOX4, and HMGA2 in breast cancer stem cells [ 108 ]. In a study of prostate cancer stem cells, Lai et al reported miR-574-5p depletion along with EZH1 and REL increased levels [ 109 ].…”

The prognostic value of abnormally expressed lncRNAs in prostatic carcinoma

“…For example, microRNA-547 has been reported to inhibit apoptosis and may be a novel prognostic and therapeutic target in the management of PCa recurrence. [ 5 ] Another microRNA, microRNA-96, was shown to promote the growth of PCa cells by suppressing MTSS1. [ 6 ] Another type of RNAs, that is, long noncoding RNAs (lncRNAs), are the focus of intensive research as current data suggest their potential in cancer diagnosis, prognosis, and therapy.…”