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.

MicroRNA-125b-2 overexpression represses ectodermal differentiation of mouse embryonic stem cells

“…The self-renewal capacity and differentiation potential are hallmarks of stem cells ( 24 ). In the past few years, miR-125b was shown to be an important factor involved in stem cell development by regulating the differentiation of stem cells ( 19 , 20 , 27 ). To evaluate the effect of miR-125b-2 on the direction of ESC differentiation, transfected and control ESCs were cultured in suspension for four days to form EBs ( 28 ).…”

The microRNA expression profile of mouse Müller glia in vivo and in vitro

“…There is much less known about the roles of miRNAs in mature glia. In glioma-derived stem cells, low miR-125 levels lead to increased proliferation due to a change in Lin-28, a target of miR-125b 50 . For the other mGliomiRs, miR-135a 40 51 , miR-23a 45 , and miR-99a 40 have been reported in astrocytes as well as for Schwann cells in the sciatic nerve along with miR-100 48 , indicating that these miRNAs could be common among glia.…”

Oncogenic mechanisms of Lin28 in breast cancer: new functions and therapeutic opportunities

“…Knockdown of Lin28 could lead to decreased level of mature miR-363, implying that Lin28 functioned as a positive regulator of miR-363 biogenesis [34]. Additionally, Lin28 could differentially promote and inhibit specific fates of cells by inhibiting miR-302d with its CSD domain [35], miR-125b could efficiently reduce Lin28 protein levels via directly binding to the 3′-UTR region of the Lin28 mRNA [36]. Intriguingly, Willbert et al have reported that Lin28 directly enhances its own expression level by binding to sites within its 3′UTR, revealing a mechanism of positive feedback regulation by Lin28 [37].…”