Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 4 de 4
2.
Oncogene ; 39(15): 3075-3088, 2020 04.
Article En | MEDLINE | ID: mdl-32066878

Accumulating evidences indicate that 3'UTR of the coding gene can act as crucial regulators in gastric cancer (GC). However, the detailed mechanisms and responsive targets are not well established. Here, we found that acvr1b gene 3'UTR (acv3UTR) was elevated in GC tissue, the expression of which was significantly correlated with advanced pTNM-stage and poor outcome in clinical patients. Forced expression of acv3UTR promoted GC cells growth in vitro and in vivo. Mechanistically, our results suggested that acv3UTR functioned as an oncogenic competing endogenous RNA via sponging miR-590-5p and enhancing YAP1 level. Tumor suppressor miR-590-5p was a molecular module in acv3UTR regulatory axis, the forced expression of which led to impairing of oncogenic potential of acv3UTR. The positive correlation of acv3UTR and YAP1 expression, and the negative correlation of acv3UTR and miR-590-5p expression, were verified in GC patients. Moreover, CFIm25 was identified as a key regulator contributing to acv3UTR aberrant expression in GC binding to UGUA-264 motif. Overall, our finding defines a mechanism for understanding the potential role of acv3UTR transcription in GC tumorigenesis, and indicates a correlation between 3'UTR trans-regulatory effect and GC development.


Adaptor Proteins, Signal Transducing/genetics , Carcinogenesis/genetics , Cleavage And Polyadenylation Specificity Factor/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , Stomach Neoplasms/genetics , Transcription Factors/genetics , 3' Untranslated Regions/genetics , Activin Receptors, Type I/genetics , Animals , Cell Line, Tumor , Cell Proliferation/genetics , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Mice , Middle Aged , RNA, Long Noncoding/metabolism , Stomach/pathology , Transcription, Genetic , Xenograft Model Antitumor Assays , YAP-Signaling Proteins
3.
Oncol Lett ; 18(1): 63-71, 2019 Jul.
Article En | MEDLINE | ID: mdl-31289473

Histone deacetylase (HDAC) inhibitors and DNA alkylators are effective components used in combination chemotherapy. In the present study, the effects of HDAC inhibitors on the expression of ATP-binding cassette (ABC) transporters were investigated. It was observed that HDAC inhibitors induced the expression of multidrug-resistant ABC transporters differently in lung cancer A549 cells than in colorectal cancer HCT116 cells. In these two cell lines, the HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) significantly increased ABCB1 expression at the mRNA and protein levels, whereas they had no evident effect on ABCG2 protein expression. SAHA and TSA decreased ABCG2 mRNA expression in A549 cells and had no evident effect on ABCG2 mRNA expression in HCT116 cells. Notably, SAHA and TSA increased the mRNA expression levels of ABCC5, ABCC6, ABCC10, ABCC11 and ABCC12, as well as the protein expression levels of ABCC2, ABCC10 and ABCC12. By contrast, these inhibitors decreased the mRNA expression levels of ABCC1, ABCC2, ABCC3 and ABCC4, as well as the expression of ABCC1 and ABCC3 proteins. Furthermore, SAHA and TSA were found to downregulate HDAC3 and HDAC4, but not HDAC1 and HDAC2. Taken together, the results suggested that HDAC inhibitors work synergistically with DNA alkylators, in part, due to the inhibitory effect of these inhibitors on ABCC1 expression, which translocates these alkylators from inside to outside of cancer cells. These results further suggested the possibility of antagonism when HDAC inhibitors are combined with anthracyclines and other ABCB1 drug ligands in chemotherapy.

4.
Med Sci Monit ; 23: 1286-1294, 2017 Mar 14.
Article En | MEDLINE | ID: mdl-28289272

BACKGROUND Angiogenic factor with G-patch and FHA domain1 (AGGF1 or VG5Q) is a newly identified human angiogenic factor. The aim of this study was to explore AGGF1 expression level in gastric cancer and detect its correlation with the prognosis. MATERIAL AND METHODS Immunohistochemistry was performed to detect AGGF1 level in gastric cancer and its adjacent noncancerous samples of 198 cases, and the relationships among the expression levels of AGGF1, vascular endothelial growth factor (VEGF), and prognosis were analyzed. RESULTS Expression of AGGF1 in gastric cancer samples was significantly higher than that in adjacent noncancerous samples (P<0.001). The overall survival rate (OS) of patients with high AGGF1 expression was significantly lower than that of patients with low AGGF1 expression (P=0.000). The Cox model analysis demonstrated that expression of AGGF1 was an independent biomarker for prediction of patients' survival in gastric cancer. CONCLUSIONS High expression of AGGF1 predicts poor prognosis in gastric cancer patients. AGGF1 can be used as an independent factor to predict postoperative survival of patients with gastric cancer.


Angiogenic Proteins/biosynthesis , Biomarkers, Tumor/biosynthesis , Stomach Neoplasms/metabolism , Adult , Aged , China/epidemiology , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Neovascularization, Pathologic/metabolism , Prognosis , Proportional Hazards Models , Stomach Neoplasms/blood supply , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Rate , Vascular Endothelial Growth Factor A/biosynthesis
...