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Abstract Background GATA binding protein 3 (GATA3) is a transcription factor that plays a critical role in the differentiation and function of luminal epithelial cells in the breast. MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression and their dysregulation has been implicated in cancer. The purpose of this study was to investigate the expression of GATA3 and its corresponding targeting miRNAs in breast cancer. Materials and methods In this study, we used bioinformatic tools, including the miRWalk database and RNA Hybrid online tool, to identify potential miRNAs that target the GATA3 mRNA. Then, we collected frozen tissue specimens from 67 breast cancer patients and 67 adjacent normal breast tissue samples and evaluated the expression levels of GATA3, hsa-miR-433-3p, and hsa-miR-144-3p using quantitative RT-PCR. Results We found that hsa-miR-433-3p and hsa-miR-144-3p are potential miRNAs that target the GATA3 mRNA, and we found that both were significantly downregulated in breast cancer tissues relative to adjacent normal breast tissues (P

Background: GATA binding protein 3 (GATA3) is a transcription factor that plays a critical role in the differentiation and function of luminal epithelial cells in the breast. MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression and their dysregulation has been implicated in cancer. The purpose of this study was to investigate the expression of GATA3 and its corresponding targeting miRNAs in breast cancer. Materials and methods: In this study, we used bioinformatic tools, including the miRWalk database and RNA Hybrid online tool, to identify potential miRNAs that target the GATA3 mRNA. Then, we collected frozen tissue specimens from 67 breast cancer patients and 67 adjacent normal breast tissue samples and evaluated the expression levels of GATA3, hsa-miR-433-3p, and hsa-miR-144-3p using quantitative RT-PCR. Results: We found that hsa-miR-433-3p and hsa-miR-144-3p are potential miRNAs that target the GATA3 mRNA, and we found that both were significantly downregulated in breast cancer tissues relative to adjacent normal breast tissues (P < 0.0001). We also observed a significant upregulation of the GATA3 mRNA in breast cancer tissues (P < 0.0001). Additionally, we found that their dysregulation was associated with clinicopathological features such as invasive carcinoma and carcinoma in situ subtypes, tumor grade, estrogen receptor status, progesterone receptor status, and HER2 status. Conclusions: Our study represents the first attempt to investigate the expression of GATA3 and its targeting miRNAs simultaneously in breast cancer. Our findings suggest that dysregulation of these genes may contribute to breast cancer development and progression. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) remains the most common and malignant tumor of the human central nervous system. Increasing evidence has highlighted that tumor cells with high transferrin receptor (TFRC) expression show advantages in growth. Long noncoding RNAs (lncRNAs) are related to glioma progression by mediating microRNAs (miRNAs). However, the underlying mechanism among TFRC, miRNA and lncRNA in GBM is limited. In the current study, we identified a new lncRNA-induced signaling mechanism that regulates the TFRC levels in GBM. The TFRC level was higher in glioma cell lines, and elevated TFRC expression promoted the proliferation and survival of glioma cells. Further study showed that hsa-miR-144a-3p bound to the 3′-UTR of TFRC mRNA and inhibited its expression, preventing the malignant properties of glioma cells, such as proliferation and survival. We also found that the lncRNA RP1-86C11.7 sponges hsa-miR-144-3p to suppress its protective role in glioma. RP1-86C11.7 overexpression in glioma cells elevated TFRC expression, increased the intracellular free iron level, and deteriorated oncogenicity, with a significant reduction in hsa-miR-144-3p. By contrast, silencing RP1-86C11.7 upregulated the hsa-miR-144-3p level, resulting in decreased TFRC expression and repressed glioma progression. However, the effect of silencing RP1-86C11.7 was reversed with simultaneous hsa-miR-144-3p inhibitor treatment: the TFRC level, intracellular iron level and proliferation in glioma cells increased. Mechanistically, our data indicated that RP1-86C11.7 exacerbates the malignant behavior of glioma through the hsa-miR-144-3p/TFRC axis. RP1-86C11.7 may be a potential biomarker or target to treat glioma in the future.

MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neurodegenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, β-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.