[Show abstract][Hide abstract] ABSTRACT: microRNAs (miRNAs or miRS) have been demonstrated to be essential for neural development. miR-125b-2, presented on human chromosome 21, is overexpressed in neurons of individuals with Down syndrome (DS) with cognitive impairments. It has been reported that miR-125b-2 promotes specific types of neuronal differentiation; however, the function of miR-125b-2 in the early development of the embryo has remained to be fully elucidated. In the present study, a mouse embryonic stem cell (mESC) line was stably transfected with a miR-125b-2 lentiviral expression vector and found that miR-125b-2 overexpression did not affect the self-renewal or proliferation of mESCs. However, miR-125b-2 overexpression inhibited the differentiation of mESCs into endoderm and ectoderm. Finally, miR-125b-2 overexpression was found to impair all-trans-retinoic acid-induced neuron development in embryoid bodies. The findings of the present study implied that miR-125b-2 overexpression suppressed the differentiation of mESCs into neurons, which highlights that miR‑125b-2 is important in the regulation of ESC differentiation. The present study provided a basis for the further identification of novel targets of miR-125b-2, which may contribute to an enhanced understanding of the molecular mechanisms of ESC differentiation.
Preview · Article · Jun 2015 · International Journal of Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: TFPI-2 (tissue factor pathway inhibitor-2) has recently been recognized as a new tumour suppressor gene. Low expression of this protein in several types of cancers allows for enhanced tumour growth, invasion and metastasis. To investigate the molecular mechanism responsible for the tumour-suppressor effects of TFPI-2, we performed yeast two-hybrid analysis and identified PSAP (prosaposin) as a TFPI-2-interacting partner. This interaction was confirmed by co-immunoprecipitation and immunofluorescence. The region of TFPI-2 that interacts with PSAP is located in the KD2 (Kunitz-type domain 2). Further study showed that PSAP does not affect the function of TFPI-2 as a serine proteinase inhibitor, but that TFPI-2 could inhibit the invasion-promoting effects of PSAP in human HT1080 fibrosarcoma cells. The results of the present study revealed that TFPI-2 interacts with PSAP, which may play an important role in the physiology and pathology of diseases such as cancer.