MiR-125b promotes cell proliferation by directly targeting Lin28 in glioblastoma stem cells with low expression levels of miR-125b

Abstract

MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs. Our previous studies have revealed that miR-125b is a typical overexpressed miRNA in human primary glioblastoma stem cells (GSCs). Here, we report that miR-125b was also found to be significantly underexpressed in three primary GSCs. Characterization of the effects of the underexpressed miR-125b in GSCs showed that elevated levels of miR-125b inhibited cell growth and induced cell cycle arrest in the G0/G1 phase in vitro; a reduction in miR-125b levels had the opposite effect on tumour growth and progression. Further research into the underlying mechanism demonstrated that miR-125b acts by targeting Lin28 to regulate cell growth. Lin28 is highly expressed in human embryonic stem cells and glioblastomas. We showed that the specific repression of Lin28 results in decreased GSC proliferation, and that the overexpression of Lin28 accelerates cell proliferation. Our results highlight a novel molecular interaction between miR-125b and Lin28, and miR-125b may represent a potential novel therapeutic agent for targeting the proliferation of GSCs. In view of our previous research showing that miR-125b was overexpressed in GSCs and functioned as an oncogene, here our finding was not in agreement with our previous report, which implies that the personalized treatment on GSCs may be necessary and important.