MiR-125a-5p functions as a tumour suppressor in breast cancer by downregulating BAP1.

MicroRNAs (miRNAs) play an important role in the regulation of human cancers, including breast cancer (BC). In the current study, we examined the expression pattern of the miRNA miR-125a-5p in human BC tissues, tumorigenesis of BC progression. We found that miR-125a-5p was significantly downregulated in human BC tissues. Overexpression of miR-125a-5p in a xenograft mouse model indicated that miR-125a-5p may function as a tumour suppressor during carcinogenesis. To explore the molecular mechanism by which miR-125a-5p contributes to BC progression, we predicted the target genes of miR-125a-5p and identified BC susceptibility gene 1-associated protein 1 (BAP1) as a direct target. Finally, we demonstrated that BAP1 had opposing effects to those of miR-125a-5p on BC cells, suggesting that miR-125a-5p may inhibit cell proliferation and promote cell apoptosis by negatively regulating BAP1. Taken together, our findings provide the first clues regarding the role of miR-125a-5p as a tumour suppressor in BC via the inhibition of BAP1 translation.

Yan L ，Yu MC ，Gao GL ，Liang HW ，Zhou XY ，Zhu ZT ，Zhang CY ，Wang YB ，Chen X ... -  《-》

lncRNA CERS6-AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR-125a-5p to upregulate BAP1 expression.

Long noncoding RNAs (lncRNAs) can act as oncogene and tumor suppressor genes in many types of cancers including breast cancer (BC). Our previous study has indicated microRNA (miR)-125a-5p was downregulated and function as a tumor suppressor in BC. However, its upstream regulation mechanism is still unclear. In this study, we used bioinformatics algorithms, RNA pulldown assay, and dual-luciferase reports assay to predict and confirm lncRNA CERS6-AS1 interacted with miR-125a-5p. Then we found CERS6-AS1 was upregulated in BC tissues. Experimental results of tumor growth in nude mice show that CERS6-AS1 promotes tumor growth. Furthermore, CERS6-AS1 regulated BC susceptibility gene 1-associated protein 1 (BAP1) expression via sponging miR-125a-5p via Western blot analysis and quantitative polymerase chain reaction arrays. Finally, we showed that miR-125a-5p had opposing effects to those of CERS6-AS1 on BC cells, demonstrating that CERS6-AS1 may promote cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p. Our results indicated CERS6-AS1 promote BC cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p to upregulate BAP1 expression.

Yan L ，Li K ，Feng Z ，Zhang Y ，Han R ，Ma J ，Zhang J ，Wu X ，Liu H ，Jiang Y ，Zhang Y ，Zhu Y ... -  《-》

The lncRNA HOXA11-AS acts as a tumor promoter in breast cancer through regulation of the miR-125a-5p/TMPRSS4 axis.

Long non-coding RNAs (lncRNAs) play vital roles in tumorigenesis. Here, we explored how lncRNA HOXA11-AS functions in the progression of breast cancer (BC). HOXA11-AS and miR-125a-5p levels were measured by a quantitative real-time polymerase chain reaction, whereas western blotting determined TMPRSS4 levels in BC tumor tissues, adjacent normal tissues and BC cell lines. The roles of HOXA11-AS, miR-125a-5p and TMPRSS4 in BC proliferation were investigated using cell counting kit-8, colony formation and flow cytometry assays, whereas scratch and transwell assays were used to measure metastasis. RNA pull-down assays and dual-luciferase assays assessed direct interactions between HOXA11-AS and miR-125a-5p. The effects of HOXA11-AS in vivo were investigated in a BC xenograft model. HOXA11-AS was upregulated in tumor tissues of 56 BC patients compared to adjacent non-tumor tissues, with high levels being associated with worse overall survival. Silencing of HOXA11-AS inhibited the proliferation and metastasis of BC cells, leading to cell cycle arrest in G0/G1 and induction of apoptosis. We identified miR-125a-5p as a target of HOXA11-AS, with miR-125a-5p inhibitors partially restoring the reduction of cell proliferation and metastasis induced by HOXA11-AS silencing. We also determined that miR-125a-5p targeted TMPRSS4 mRNA, with HOXA11-AS knockdown and miR-125a-5p mimics suppressing TMPRSS4. Overexpression of TMPRSS4 partially compensated for the reduction of cell proliferation and metastasis induced by HOXA11-AS silencing. Finally, we confirmed the mechanism of HOXA11-AS in the regulation of tumorigenesis in the mouse model. HOXA11-AS regulates the tumorigenic ability of BC via the miR-125a-5p/TMPRSS4 axis. This provides insights for regulatory mechanisms involved in BC progression, and may enable new treatment strategies in the clinical setting.

Xu Y ，Ren Z ，Wang X ，Ren M ... -  《-》

MicroRNA-125a-5p plays a role as a tumor suppressor in lung carcinoma cells by directly targeting STAT3.

Zhong L ，Sun S ，Shi J ，Cao F ，Han X ，Chen Z ... -  《-》

Suppression of microRNA-125a-5p upregulates the TAZ-EGFR signaling pathway and promotes retinoblastoma proliferation.

Retinoblastoma is the most common intraocular malignancy that occurs during childhood; however, the mechanism underlying retinoblastoma proliferation and progression remains unclear. MicroRNAs (miRNAs) play an important role in the regulation of a myriad of biological processes in various types of cancer. In this study, we performed microarray analysis followed by qRT-PCR using four classes of retinoblastoma tissues with increasing cTNM classification stages to identify crucial miRNAs whose expression was correlated with retinoblastoma progression. miR-125a-5p was downregulated, and its expression levels were inversely correlated with cell proliferation in retinoblastoma compared with adjacent non-tumor retinal tissues. The overexpression of miR-125a-5p significantly suppressed cell proliferation and tumor formation in retinoblastoma. We further identified the transcriptional co-activator with PDZ binding motif (TAZ) as a direct target of miR-125a-5p. Importantly, TAZ levels were inversely correlated with miRNA-125a-5p expression, and TAZ promoted retinoblastoma cell proliferation. Moreover, the overexpression of miR-125a-5p led to a decrease in TAZ expression and downstream EGFR signaling pathway activation both in vitro and vivo. Finally, TAZ overexpression in retinoblastoma cells overexpressing miR-125a-5p restored retinoblastoma cell proliferation and EGFR pathway activation. Taken together, our data demonstrated that miR-125a-5p functions as an important tumor suppressor that suppresses the EGFR pathway by targeting TAZ to inhibit tumor progression in retinoblastoma. Thus, the miR-125a-5p/TAZ/EGFR axis may be a potential therapeutic target for retinoblastoma.

Zhang Y ，Xue C ，Zhu X ，Zhu X ，Xian H ，Huang Z ... -  《-》