Hsa‑miR‑376c‑3p targets Cyclin D1 and induces G1‑cell cycle arrest in neuroblastoma cells

Abstract

High-risk neuroblastoma is the most aggressive form of cancer in children. The estimated survival of children with high-risk neuroblastoma is 40-50% compared with low and intermediate risk neuroblastoma, which is >98 and 90-95%, respectively. In addition, patients with high-risk neuroblastoma often experience relapse following intensive treatments with standard chemotherapeutic drugs. Therefore alternative strategies are required to address this problem. MicroRNAs (miRNAs/miRs) are small, endogenously expressed non-coding RNAs, which when deregulated have been demonstrated to serve significant roles in the tumorigenesis of a number of different types of cancer. Results from a previous deep sequencing study identified 22 downregulated miRNAs from the 14q32 miRNA cluster differentially expressed in neuroblastoma cell lines isolated from 6 patients at diagnosis and at relapse following intensive treatments. miR-376c-3p is one of the 22 miRNAs that was downregulated in the majority of the cell lines isolated from patients post treatment. The present study employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to quantify the basic expression of miR-376c-3p in 6 neuroblastoma cell lines. The functional role of miR-376c-3p in the neuroblastoma cell lines was evaluated by alamar blue-cell viability and propidium iodide-flow cytometric assays. In addition, luciferase reporter assays, RT-qPCR and western blotting were performed to identify and quantify the targets of miR-376c-3p in neuroblastoma cell lines. Ectopic expression of miR-376c-3p led to significant inhibition of cell viability and G1-cell cycle arrest in multiple neuroblastoma cell lines by reducing the expression of cyclin D1, an oncogene critical for neuroblastoma pathogenesis. The results of the present study provide novel insights into the functional role of miR-376c-3p and suggest new approaches for the treatment of neuroblastoma.

miR‑376c‑3p modulates the properties of breast cancer stem cells by targeting RAB2A

“…1B). The correlation analysis indicated that low miR-376c-3p expression was significantly correlated with lymph node metastasis (P=0.002; Table SI), which was consistent with previous studies that demonstrated that miR-376c-3 served as a cancer suppressor (22)(23)(24)(25). Among the potential targets of miR-376c-3ppredicted using online software TargetScan (http://www.targetscan.org/vert_72/), RAB2A has been reported to be involved in breast cancer development (28,29).…”

“…1A). Among the miRNAs, miR-376c-3p has been reported to participate in the development of several types of cancer (22)(23)(24)(25)(26)(27), and is downregulated in breast cancer (33)(34)(35)(36). However, how miRNAs affect breast cancer progression is not completely understood.…”

“…Moreover, miR-376c-3p negatively regulates gastric tumour growth by modulating the expression of BCL2 associated agonist of cell death (BAD) and Smad4 (23). miR-376c-3p also suppresses cell proliferation and induces apoptosis in oral squamous cancer cells and neuroblastoma cells by targeting homeobox B7 (24) and Cyclin D1 (25), respectively. However, another study reported that miR-376c-3p facilitates hepatocellular carcinoma progression by inhibiting AT-rich interaction domain 2 expression (26).…”

CircPIP5K1A facilitates gastric cancer progression via miR-376c-3p/ZNF146 axis

“…Mechanically, we speculated that circPIP5K1A might post-transcriptionally modulate gene expression by functioning as a ceRNA in GC based on the data that circPIP5K1A was mainly distributed in cytoplasm, and thereby it was primarily needed to find out the specific miRNA. Subsequently, through bioinformatics prediction and molecular experiments, miR-376c-3p was screened out due to its notable high binding ability with circPIP5K1A and its close association with the progression of human malignancies [25][26][27]. Then miR-376c-3p was confirmed to be dramatically downregulated in GC cells.…”

Cross-sectional study of human coding- and non-coding RNAs in progressive stages of Helicobacter pylori infection

“…www.nature.com/scientificdata www.nature.com/scientificdata/ (expressed in arbitrary fluorescence units). Quantitative N 0 values have been used in previous publications [19][20][21][22][23][24] . Determining N 0 has several advantages over relative quantification.…”