12q22

MIRN331,hsa-mir-331,mir-331

Prostate cancer

Five references have suggested a tumour suppressor role for miR-331 in prostate cancer. The first report demonstrated downregulation of miR-331-3p in prostate cancer, and showed that this promoted ERBB-2 expression and AKT activity. Restoring miR-331-3p to prostate cancer cell lines reduced androgen receptor (AR) pathway signaling and PSA expression. Another report confirmed the reduced expression of miR-331-3p in aggressive prostate cancers. Two other studies showed that the RNA-binding protein HuR induces ERBB-2 expression in prostate cancer by preventing the degradation of ERBB-2 mRNA by miR-331-3p, and that miR-331-3p inhibits the growth of prostate cancer cells in part by repressing expression of the deoxyhypusine hydroxylase (DOHH), an enzyme that controls the activity of the eukaryotic translation initiation factor eIF5A. In the latter study, an inverse correlation between miR-331-3p and DOHH expression was observed in human prostate cancer tissues. A fifth publication confirmed that miR-331-3p is a prostate cancer tumour suppressor via its regulation of KLK4 expression in prostate cancer cells.

Leukaemia

Two references implicate miR-331 in leukaemia. One report showed that the levels of of miR-331-5p were inversely correlated with expression of P-glycoprotein, a drug resistance factor, in leukaemia cell lines with variable resistance to doxorubicin, and that transfection of these cell lines with miR-331-5p increased their sensitivity to doxorubicin. Lower levels of miR-331-5p were also detected in patients following treatment relapse. A second study reported that miR-331 was overexpressed in acute lymphocytic leukaemia (ALL) and chronic lymphocytic leukaemia (CLL), and it was speculated that miR-331 might have roles in haematopoiesis and leukaemogenesis by promoting STAT activation through its regulation of the mRNA target SOCS1.

Gastric cancer

One reference has suggested that miR-331-3p is a gastric cancer tumour suppressor. miR-331-3p was downregulated in gastric cancer cell lines, where transient overexpression of miR-331-3p reduced E2F1 expression and blocked cell cycle progression.

Liver cancer

Increased circulating levels of miR-331 in a rat model of hepatocarcinogenesis suggest that miR-331 may have utility as a biomarker for the development and/or progression of liver cancer.

Asbestos-related lung cancer

One report identified miR-331-3p in a set of overexpressed miRNAs in asbestos-related lung cancer, suggesting that it might have diagnostic use.

Natural killer (NK) cell activation

Activation of NK cells by IL-2, IL-15 and IL-21 was shown to regulate expression of specific miRNAs in NK cells, including miR-331-3p. This suggested that miR-331-3p may have a role in the activation of NK cells.

Cerebral ischaemia

miR-331 expression in cerebral ischaemia was regulated by the mood stabiliser and histone deacetylase inhibitor valproic acid (VPA), suggesting that it may have a role in this disease process.