RY, MHL, XG, SG and MY participated in the experiments and drafted the manuscript
August 11, 2021
RY, MHL, XG, SG and MY participated in the experiments and drafted the manuscript. miR-138-5p to the target gene BIRC5. We also investigated the biological role of miR-138-5p targeting to Survivin in bladder malignancy cell lines SGC 707 both and via cell proliferation and invasion assays and using a mouse xenograft tumor model. We exhibited that BIRC5 repression by miR-138-5p suppressed the proliferative and invasive characteristics of bladder malignancy cells and that miR-138-5p exerted an anti-tumor effect by negatively regulating BIRC5 in a xenograft mouse model. Conclusions Taken together, our findings provide the first clues regarding the role of miR-138-5p as a tumor suppressor in bladder malignancy by inhibiting BIRC5 translation. Electronic supplementary material The online version of this article (doi:10.1186/s12943-016-0569-4) contains supplementary material, which is available to authorized users. results (Fig.?4h). Furthermore, hematoxylin and eosin (H&E) staining of xenograft tissues showed confluent necrotic areas and reduced cell mitosis in the group implanted with the cells expressing the miR-138-5p lentiviral vector compared with the control group, whereas an increase in cell mitosis was observed in the xenografts from your BIRC5 overexpression group (Fig.?4i). Xenografts with both miR-138-5p and BIRC5 overexpression exhibited increased cell mitosis compared to xenografts with only miR-138-5p overexpression (Fig.?4i), suggesting that Survivin overexpression could attenuate the anti-proliferative effect of miR-138-5p. Immunohistochemical staining SGC 707 also revealed the presence of lower levels of Survivin in tumors from mice implanted with miR-138-5p-overexpressing cells, whereas the tumors from your BIRC5-overexpressing mice showed increased Survivin protein levels. Tumors with both miR-138-5p and BIRC5 overexpression exhibited increased Survivin protein levels compared to xenografts with only miR-138-5p overexpression (Fig.?4i and ?andk).k). Finally, the proliferative activity of the tumor cells SGC 707 was assessed by immunocytochemistry with the mouse monoclonal antibody targeting Ki-67. The cell proliferation rate as indicated by the percentage of Ki-67-positive tumor cells was increased in the group implanted with cells made up of the BIRC5 plasmid and decreased in the group implanted with cells made up of the miR-138-5p lentiviral vector. Similarly, BIRC5 overexpression attenuated the pro-proliferative effect caused by miR-138-5p overexpression (Fig.?4, i and j). These results were consistent with the findings of the assays, which strongly validated the role of miR-138-5p as a tumor suppressor by targeting BIRC5. Conversation Survivin is an oncogene that regulates the apoptosis, proliferation, and invasion of many cancers, including bladder malignancy [16C19]. Survivin has been recognized as a highly specific biomarker for bladder malignancy and its expression is relative to the presence, stage, progression and mortality of bladder malignancy . As a tumor biomarker, Survivin protein is highly expressed in bladder tumors and either absent or weakly SGC 707 expressed in the normal adjacent bladder mucosa . Interestingly, we found that the Survivin mRNA was detectable in normal bladder tissue and did not differ as much as the protein levels between bladder malignancy and normal adjacent bladder mucosa. The discordance between Survivin protein and mRNA in bladder malignancy suggested that post-transcriptional regulation might be involved in Survivin protein expression. One essential mode of post-transcriptional regulation is the repression of mRNA transcripts by miRNA. miRNAs regulate gene expression by the sequence-selective targeting of mRNAs, leading to either translational repression or mRNA degradation [8, 22]. It was reported that miRNAs related to post-transcriptional regulation play an important role in Survivin dysregulation in some human cancers . However, there is limited information about the miRNA regulation of Survivin expression in bladder malignancy. In this study, we searched for miRNAs that can target Survivin and recognized miR-138-5p as a candidate. We experimentally validated the direct inhibition of Survivin translation by miR-138-5p by overexpressing and Mmp28 knocking down miR-138-5p in bladder malignancy cells. In addition, we showed that in cultured bladder malignancy cells, miR-138-5p inhibited Survivin expression as well as cell proliferation and invasion; furthermore, miR-138-5p also slowed tumor growth in a xenograft mouse model. The results exhibited a novel regulatory network including miR-138-5p and Survivin to fine-tune the proliferation and.