ABSTRACT
MicroRNA miR-302 has been found to induce some tumor cell lines to "transdifferentiate" into miRNA-induced pluripotent stem cells (mirPS), thereby inhibiting tumor cell proliferation and reducing tumorigenicity. This study firstly found that miR-302 inhibited the proliferation and migration of endometrial cell line, Ishikawa and HEC-1-B, and arrested cell cycle at the G2/M phase. In addition, miR-302 inhibited tumorigenicity in immunodeficient mice transplanted with Ishikawa cells. Microarray and Western blotting results showed that miR-302 significantly inhibited CDK1 and Cyclin D1 gene expression in Ishikawa cells. MiR-302 directly targeted Cyclin D1, but indirectly regulated CDK1 gene expression.
Subject(s)
Cyclin D1/antagonists & inhibitors , Cyclin-Dependent Kinase Inhibitor p57/antagonists & inhibitors , Endometrial Neoplasms/therapy , Genetic Therapy/methods , MicroRNAs/administration & dosage , Animals , Cell Growth Processes/genetics , Cell Line, Tumor , Cell Movement/genetics , Cyclin D1/genetics , Cyclin D1/metabolism , Cyclin-Dependent Kinase Inhibitor p57/genetics , Cyclin-Dependent Kinase Inhibitor p57/metabolism , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Female , Gene Expression Profiling , Humans , Mice , Mice, Nude , MicroRNAs/genetics , Signal Transduction , Transfection/methods , Xenograft Model Antitumor AssaysABSTRACT
The molecular mechanism responsible for the regulation of GDNF in Sertoli cells remains largely unknown. In the present study, FSH induced the expression of Nur77 and GDNF in mouse testis tissue and human fetal Sertoli cells. Moreover, FSH increased the number of A spermatogonia co-cultured with Sertoli cells. In the additional assays, Nur77 was observed to directly regulate GDNF transcription. Furthermore, overexpression of Nur77 and siRNA-mediated knockdown of Nur77 affected levels of GDNF mRNA and protein in primary human fetal Sertoli cells. These results indicate that FSH-induced Nur77 regulates the expression of GDNF in Sertoli cells to stimulate the proliferation of A spermatogonia in vitro.
