Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant hair disorder. Through the study of a mouse model, we identified a mutation in the 5'-untranslated region of the hairless (HR) gene in patients with MUHH in a Caucasian family. The corresponding mutation, named 'hairpoor', was found in mutant mice that were generated through N-ethyl-N-nitrosourea mutagenesis. Hairpoor mouse mutants display partial hair loss at an early age and progress to near alopecia, which resembles the MUHH phenotype. This mutation conferred overexpression of HR through translational derepression and, in turn, decreased the expression of Sfrp2, an inhibitor of the Wnt signaling pathway. This study indicates that the gain in function of HR also results in alopecia, as seen with the loss of function of HR, via abnormal upregulation of the Wnt signaling pathway.
Colorectal cancer (CRC), one of the most prevalent malignant cancers, has high rates pf incidence and is the fourth leading cause of cancer-related deaths for both men and women worldwide. MicroRNAs (miRNAs) play critical roles in the development of various types of cancers. miRNA‑330-5p has been implicated in the progression of prostate, neuronal and pancreatic cancers by regulating proliferation, migration, invasion and epithelial-mesenchymal transition of cells. The purpose of the present study was to investigate the expression of miR-330-5p in CRC and identify its target gene(s) that may act in CRC tumorigenesis. We found that miR-330-5p expression was significantly lower in CRC tissues than that in adjacent non-tumorous tissues. Furthermore, we identified integrin α5 (ITGA5) as a new target of miR-330-5p and found that it inhibits ITGA5 expression by directly binding to the 3' untranslated region of ITGA5 mRNA. These results suggest that downregulation of miR-330-5p expression may affect CRC development via modulation of ITGA5 expression.
Colorectal cancer (CRC), the third most common cancer worldwide, also has the
highest rate of cancer-related morbidity and mortality. WNT signaling is
initiated by binding of WNT to various receptors, including frizzleds (FZDs),
and plays a critical role in CRC and other tumor development by regulating
proliferation, differentiation, migration, apoptosis, and polarity. Among the
members of the FZD family, FZD6 is broadly expressed in various tissues, and its
overexpression has been reported in several cancers, suggesting an important
role in cancer development. In this study, we investigated the expression of
FZD6 in patients with CRC and found it to be increased in tumors, as compared to
paired adjacent non-tumor tissues. Additionally, we found that FZD6 expression
was negatively regulated by miR199a5p in CRC cells. These results suggest that
overexpression of FZD6, mediated by reduced expression of miR-199a-5p, may play
an important role in the development of CRC. [BMB Reports 2015; 48(6):
360-366]
Recently, we reported a novel therapeutic probiotic-derived protein, p8, which has anti-colorectal cancer (anti-CRC) properties. In vitro experiments using a CRC cell line (DLD-1), anti-proliferation activity (about 20%) did not improve after increasing the dose of recombinant-p8 (r-p8) to >10 μM. Here, we show that this was due to the low penetrative efficiency of r-p8 exogenous treatment. Furthermore, we found that r-p8 entered the cytosol through endocytosis, which might be a reason for the low penetration efficiency. Therefore, to improve the therapeutic efficacy of p8, we tried to improve delivery to CRC cells. This resulted in endogenous expression of p8 and increased the anti-proliferative effects by up to 2-fold compared with the exogenous treatment (40 μM). Anti-migration activity also increased markedly. Furthermore, we found that the anti-proliferation activity of p8 was mediated by inhibition of the p53-p21-Cyclin B1/Cdk1 signal pathway, resulting in growth arrest at the G2 phase of the cell cycle. Taken together, these results suggest that p8 is toxic to cancer cells, shows stable expression within cells, and shows strong cancer suppressive activity by inducing cell cycle arrest. Therefore, p8 is a strong candidate for gene therapy if it can be loaded onto cancer-specific viruses.
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