MicroRNA-199a-3p suppresses the invasion and metastasis of nasopharyngeal carcinoma through SCD1/PTEN/AKT signaling pathway.

MicroRNAs (miRs) are 18-25 nucleotides non-coding RNAs, which contribute to tumorigenesis. Previous studies have demonstrated that miR-199a-3p is dysregulated in human nasopharyngeal carcinoma (NPC), but its role in NPC progression still largely unknown. The current study aimed to determine the potential role of miR-199a-3p in NPC progression and the underlying mechanisms. In this study, miR-199a-3p was found to be prominently down-regulated in NPC tissues and cells. The cellular assay showed that transfection of miR-199a-3p markedly repressed the migration, invasion and induced epithelial-mesenchymal transition (EMT) in both 5-8F and CNE-2 cell lines. By dual-luciferase reporter, western blotting and gas chromatography assays, we found that SCD1 is not only highly expressed in NPC tissues and negatively associated with the prognosis of NPC patients but also can be apparently downregulated by miR-199a-3p in NPC cells, suggesting that SCD1 is a direct target gene of miR-199a-3p. Moreover, inhibition of miR-199a-3p expression activated PI3K/Akt signaling and up-regulated the expression of MMP-2. With tumor xenograft models in nude mice, we also showed that miR-199a-3p repressed tumor growth in vivo. Our study demonstrated that miR-199a-3p inhibited migration and invasion of NPC cells through downregulating SCD1 expression, thus providing a potential target for the treatment of NPC.

Hu W ，Wang Y ，Zhang Q ，Luo Q ，Huang N ，Chen R ，Tang X ，Li X ，Luo H ... -  《-》

miR-144-3p facilitates nasopharyngeal carcinoma via crosstalk with PTEN.

This study aims to investigate the role of miR-144-3p and phosphatase and tensin homolog (PTEN) in nasopharyngeal carcinoma (NPC), along with their crosstalk with the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) pathway. Quantitative reverse transcription polymerase chain reaction and western blot were used to measure the gene expression at the transcriptional and translational levels. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay were used to examine cell proliferation via standard protocol. Transwell assay was conducted to examine cell invasiveness. A flow cytometer was used to determine cell apoptosis. Dual-Luciferase Reporter Gene Assay (SLDL-100) was used to confirm the target relationship between miR-144-3p and PTEN. Xenografts were used to detect the in vivo effects of the molecules of interest. miR-144-3p was significantly overexpressed, whereas PTEN was more underexpressed in tumor tissues than in adjacent tissues. miR-144-3p promoted the proliferation and invasion of NPC cells and inhibited apoptosis by directly targeting PTEN, which improves PI3K-Akt signaling. miR-144-3p forced epithelial-mesenchymal transition in NPC. miR-144-3p promotes the progression of NPC by directly targeting PTEN via crosstalk with PI3K-Akt signaling.

Song L ，Chen L ，Luan Q ，Kong Q ... -  《-》

HIF-1α downregulation of miR-433-3p in adipocyte-derived exosomes contributes to NPC progression via targeting SCD1.

Resident adipocytes under a hypoxic tumor microenvironment exert an increasingly important role in cell growth, proliferation, and invasion in cancers. However, the communication between adipocytes and cancer cells during nasopharyngeal carcinoma (NPC) progression is poorly understood. Here, we demonstrate that hypoxic adipocyte-derived exosomes are key information carriers that transfer low expression of miR-433-3p into NPC cells. In addition, luciferase reporter assays detected that hypoxia inducible factor-1α (HIF-1α) induced miR-433-3p transcription through five binding sites at its promoter region. Concordantly, the low expression of miR-433-3p promoted proliferation, migration, and lipid accumulation in NPC cells via targeting stearoyl-CoA desaturase 1 (SCD1) are suggested by functional studies. Consistent with these findings, in tumor-bearing mice, NPC cells with low HIF-1α expression, high miR-433-3p expression, and low SCD1 expression were equally endowed with remarkably reduced potential of tumorigenesis. Collectively, our study highlights the critical role of the HIF-1α-miR-433-3p-SCD1 axis in NPC progression, which can serve as a mechanism-based potential therapeutic approach.

Yin H ，Qiu X ，Shan Y ，You B ，Xie L ，Zhang P ，Zhao J ，You Y ... -  《-》

miR-205-5p regulates epithelial-mesenchymal transition by targeting PTEN via PI3K/AKT signaling pathway in cisplatin-resistant nasopharyngeal carcinoma cells.

Epithelial-mesenchymal transition (EMT) symbolizes the predominant program of advanced-stage cancer, it is critical in cancer progression, metastasis, and chemotherapy resistance. In this study, the metastatic properties of nasopharyngeal carcinoma (NPC) cells were evaluated by morphological examination, wound healing assay, migration and invasion assay. Western blotting and qRT-PCR were used to ascertain the expression of markers which were associated with EMT. The effects of miR-205-5p on invasion, migration, EMT and proliferation of NPC cells were evaluated and the molecular mechanisms of their interaction were explored. In this study, we manifested firstly that the expression of miR-205-5p in cisplatin-resistant NPC cell line HNE1/DDP was obviously up-regulated than that in its parental cell line HNE1. Then we analyzed the specific role of miR-205-5p through functional assays by transfecting specific mimics and inhibitors. The results indicated that low expression of miR-205-5p restrained EMT progression of HNE1/DDP cells. Further studies on the mechanism of miR-205-5p manifested that PTEN was a downstream candidate gene of miR-205-5p, down-regulated PTEN expression could counteract the effect of miR-205-5p inhibitors, and the regulation of EMT by miR-205-5p on HNE1/DDP cells depended on the PI3K/AKT signaling pathway. Overall, our results indicated that miR-205-5p was targeting PTEN to regulate EMT through the PI3K/AKT pathway. This study will supply a new treatment target for advanced NPC.

Zhang P ，Lu X ，Shi Z ，Li X ，Zhang Y ，Zhao S ，Liu H ... -  《-》

MiR-155 promotes proliferation and inhibits apoptosis of nasopharyngeal carcinoma cells through targeting PTEN-PI3K/AKT pathway.

Zuo WN ，Zhu H ，Li LP ，Jin AY ，Wang HQ ... -  《-》