We intend to evaluate the expression, clinical relevance, and functional role of microRNA-137 (miR-137) in human cervical cancer (CC). MiR-137 expressions were assessed by qPCR in CC cell lines and human CC tumors. The correlation between endogenous miR-137 expression and CC patients' postoperative overall survival was examined statistically. CC cell lines, Ca-Ski, and SiHa cells were transduced with lentivirus to ectopically upregulate endogenous miR-137 expressions. Possible inhibitory effects of miR-137 upregulation on CC in vitro proliferation and migration, as well as in vivo transplantation were evaluated. Targeting of enhancer of zeste homolog 2 (EZH2) gene by miR-137 in CC was assessed by dual-luciferase activity assay and qPCR. In CC cells with upregulated miR-137,
Background: Retinoblastoma (RB) is a common malignancy in children eyes. Aberrant microRNA (miR) expression is observed in many cancer cases. miR-515-5p is reported to be concerned with the course of many cancers. This study explores the role of miR-515-5p in proliferation and drug sensitivity of RB cells. Methods: Human RB cell lines (WERI-RB1, SO-RB50 and Y79) and human retinal pigment epithelial cell line ARPE-19 were utilized in this study. Drug-resistant cells SO-RB50/VCR and SO-RB50/CBP were constructed for the following experiments. The expressions of miR-515-5p and Notch1 in RB cells were detected. Notch1 was significantly upregulated in RB cells while miR-515-5p was notably downregulated. Then, the binding relationship between miR-515-5p and Notch1 was predicted and verified. Results: miR-515-5p negatively regulated Notch1 expression. In vitro and in vivo experiments revealed that overexpressed miR-515-5p inhibited RB cell proliferation and enhanced drug sensitivity. Functional rescue experiment suggested that miR-515-5p regulated RB cell proliferation and drug sensitivity via inhibiting Notch1 expression. Conclusion: It could be concluded that overexpressed miR-515-5p suppressed proliferation and drug resistance of RB cells by targeting Notch1 expression, indicating that miR-515-5p might constitute a promising therapy target for RB.
Background:
The oncoprotein binding (OPB) domain of Yin Yang 1 (YY1) consists of
26 amino acids between G201 and S226, and is involved in YY1 interaction with multiple oncogene
products, including MDM2, AKT, EZH2 and E1A. Through the OPB domain, YY1 promotes the
oncogenic or proliferative regulation of these oncoproteins in cancer cells. We previously demonstrated
that a peptide with the OPB sequence blocked YY1-AKT interaction and inhibited breast
cancer cell proliferation.
Objective:
In the current study, we characterized the OPB domain and determined a minimal region
for peptide design to suppress cancer cell
Methods:
Using alanine-scan method, we identified that the amino acids at OPB C-terminal are essential
to YY1 binding to AKT. Further studies suggested that serine and threonine residues, but not
lysines, in OPB play a key role in YY1-AKT interaction. We generated GFP fusion expression vectors
to express OPB peptides with serially deleted N-terminal and found that OPB1 (i.e. G201-S226)
is cytoplasmic, but OPB2 (i.e. E206-S226), OPB3 (i.e. E206-S226) and control peptide were both
nuclear and cytoplasmic.
Results:
Both OPB1 and 2 inhibited breast cancer cell proliferation and migration, but OPB3 exhibited
similar effects to control. OPB1 and 2 caused cell cycle arrest at G1 phase, increased p53 and p21 expression,
and reduced AKT(S473) phosphorylation in MCF-7 cells, but not in MDA-MB-231 cells.
Conclusion:
: Overall, the serines and threonines of OPB are essential to YY1 binding to oncoproteins,
and OPB peptide can be minimized to E206-S226 that maintain inhibitory activity to YY1-
promoted cell proliferation.
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