Altogether, this study unveils a prometastatic role of the IFNγ pathway via a new mechanism of action, which raises concerns about its clinical application.<b>Significance:</b> A unique IFIT5-XRN1 complex involved in the turnover of specific tumor suppressive microRNAs is the underlying mechanism of IFNγ-induced epithelial-to-mesenchymal transition in prostate cancer.<i>See related commentary by Liu and Gao, p. 1032</i>.
The biphasic effects of IFNγ in prostate cancer raise concerns about its therapeutic application, which need to be evaluated in future studies.<i>See related article by Lo et al., p. 1098</i>.
Minor alleles of rs2243250 (T) in IL4 (OR = 1.46, 95% CI 1.03-2.08, P-trend = 0.03), rs1800896 (G) in IL10 (OR = 0.77, 95% CI 0.61-0.96, P-trend = 0.02), rs2430561 (A) in IFNG (OR = 1.33, 95% CI 1.02-1.74; P-trend = 0.04), rs3747531 (C) in MSR1 (OR = 0.55, 95% CI 0.32-0.95; P-trend = 0.03), and possibly rs4073 (A) in IL8 (OR = 0.81, 95% CI 0.64-1.01, P-trend = 0.06) were associated with higher- (Gleason 7-10; N = 222), but not lower- (Gleason 2-6; N = 380) grade prostate cancer.
By mechanistic investigations we showed that miR-221 regulates cell growth, invasiveness, and apoptosis in prostate cancer at least partially via STAT1/STAT3-mediated activation of the JAK/STAT signaling pathway. miR-221 directly inhibits the expression of SOCS3 and IRF2, two oncogenes that negatively regulate this signaling pathway. miR-221 expression sensitized prostate cancer cells for IFN-γ-mediated growth inhibition.
MUC1 expression was evaluated in normal prostate epithelial cells (PrEC), and prostate cancer cell lines in response to dihydrotestosterone (DHT), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) treatment.
Interferon-gamma and its functional receptors overexpression in benign prostatic hyperplasia and prostatic carcinoma: parallelism with c-myc and p53 expression.
Interferon-gamma (IFN-gamma) production by peripheral blood leukocytes from bladder cancer patients was compared with that of patients with prostate cancer and benign prostatic hyperplasia, nontumor-bearing patients with bacterial infections, and normal controls.