94241

TP53INP1

It has been shown that acquisition of epithelial-mesenchymal transition (EMT) and induction of cancer stem cell (CSC)-like properties contribute to metastasis of cancers in many studies; however, the molecular mechanisms underlying EMT and CSC phenotypes in liver cancer cells remain to be elucidated. MiR-155 is an important microRNA associated with tumour progression. Here, we report that miR-155 regulates not only the epithelial-mesenchymal transition but also the stem-like transition in liver cancer cells. Utilizing quantitative RT-PCR, we found that the expression of miR-155 is positively related to the levels of CD90, CD133 and Oct4 in enriched spheres. Up-regulated miR-155 significantly increases the population of stem-like CSCs among liver cancer cells and the ability to form tumour spheres. Additionally, miR-155 overexpression in cells significantly increases cell motility and invasion, as well as the epithelial-mesenchymal transition process. Conversely, suppression of miR-155 in cells had an opposite effect, which was partially rescued by the down-regulation of TP53INP1. Collectively, miR-155 promotes liver cancer cell EMT and CSCs, in part, via silencing TP53INP1. In addition, we found that TGF-beta1 indirectly regulates TP53INP1 expression via miR-155 in liver cancer cells. Taken together, our findings suggest that miR-155 regulates TP53INP1 expression, to induce the epithelial-mesenchymal transition and acquisition of a stem cell phenotype.CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVES: To explore the effects of the competitive endogenous RNA (ceRNA) network between TP53INP1 and E-cadherin on the invasion and migration of glioma. RESULTS: TP53INP1 and E-cadherin mRNA and protein were significantly overexpressed in normal brain tissues compared with glioma tissue specimens and correlated with the grades of glioma negatively. The expression of TP53INP1 and E-cadherin were correlated positively. Patients with higher TP53INP1 or E-cadherin expression had longer overall survival. Moreover, TP53INP1 3'-UTR inhibited glioma cell proliferation, invasion and proliferation; Furthermore, the 3'-UTRs of TP53INP1 and E-cadherin harboured seven identical miRNAs binding sites, and TP53INP1 3'-UTR could increase the expression of E-cadherin and decrease the expression of vimentin thus repressing the epithelial-mesenchymal transition (EMT). However, the coding sequence of TP53INP1 could not increase the expression of E-cadherin and the inhibitory effect on EMT of TP53INP1 3'-UTR was reversed by the siRNA against Dicer. CONCLUSIONS: TP53INP1 3'-UTR could inhibit the EMT, thus hindering the migration and invasion of glioma via acting as a ceRNA for E-cadherin.

Paclitaxel is a firstline chemotherapeutic agent for gastric cancer; however, resistance limits its effectiveness. Investigation into the underlying mechanisms of paclitaxel resistance is urgently required. In the present study, a paclitaxelresistant gastric cancer cell line (MGC803R) was generated with a morphological phenotype of epithelialtomesenchymal transition (EMT) and increased expression levels of microRNA (miR)1555p. MGC803R cellderived exosomes were effectively taken up by paclitaxelsensitive MGC803S cells, which exhibited EMT and chemoresistance phenotypes. miR1555p was enriched in MGC803Rexosomes and could be delivered into MGC803S cells. miR1555p overexpression in MGC803S cells via transfection with mimics resulted in similar phenotypic effects as treatment with MGC803R exosome and increased miR1555p content in MGC803S exosomes, which then capable of inducing the malignant phenotype in the sensitive cells. GATA binding protein 3 (GATA3) and tumor protein p53inducible nuclear protein 1 (TP53INP1) were identified as targets of miR1555p. Exosomal miR1555p inhibited these targets by directly targeting their 3' untranslated regions. Knockdown of miR1555p was observed to reverse the EMT and chemoresistant phenotypes of MGC803R cells, potentially via GATA3 and TP53INP1 upregulation, which inhibited MGC803Rexosomes from inducing the malignant phenotype. These results demonstrated that exosomal delivery of miR1555p may induce EMT and chemoresistant phenotypes from paclitaxelresistant gastric cancer cells to the sensitive cells, which may be mediated by GATA3 and TP53INP1 suppression. Targeting miR1555p may thus be a promising strategy to overcome paclitaxel resistance in gastric cancer.