Interaction of hsa-miR-381 and glioma suppressor LRRC4 is involved in glioma growth

LRRC4 is not only a brain-specific gene, but it has also been identified as a tumor suppressor gene for glioma. Promoter methylation of LRRC4 is frequently involved in the inactivation in glioma. MiRNA-mediated gene regulation has recently been demonstrated to play an important role in multiple biological processes related to cancer, including glioma. In this study, we demonstrated that a small regulatory microRNA, hsa-miR-381, an “oncomir”, had a major role in glioma progression and that LRRC4 was a target of hsa-miR-381. By regulating LRRC4, hsa-miR-381 increased the in vitro and in vivo proliferation of glioma cells, and this action was associated with decreased inhibition of MEK/ERK and AKT signaling. Conversely, LRRC4, as a glioma suppressor, inhibited the endogenous expression of hsa-miR-381 and decreased cell proliferation and tumor growth. The interaction of hsa-miR-381 and LRRC4 is involved in the pathogenesis of glioma. In addition, the stable expression of hsa-miR-381 in blood provides a novel and promising diagnostic biomarker, and anti-hsa-miR-381 “antagomir” may be an ideal target for glioma therapy.

Research highlights
► We demonstrate that LRRC4 is a target of miR-381.
► MiR-381 can increase proliferation of glioma cells through the ERK and AKT signaling.
► LRRC4 inhibits the expression of miR-381 and decreases glioma cell proliferation.
► The expression of miR-381 in blood provides a novel promising diagnosis biomarker.