MicroRNA-19a promotes nasopharyngeal carcinoma by targeting transforming growth factor β receptor 2

Abstract

MicroRNA (miR), a class of small non-coding RNA, function as key regulators in gene expression through directly binding to the 3′ untranslated region of their target mRNA, which further leads to translational repression or mRNA degradation. miR-19a, a member of miR-17-92 cluster, has an oncogenic role in a variety of malignant tumors. However, the exact role of miR-19a in nasopharyngeal carcinoma (NPC) has not previously been studied. The present study aimed to investigate the function and mechanism of miR-19a in regulating the viability and invasion of NPC cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) data indicated that the expression levels of miR-17-92 cluster members (miR-17, miR-18a, miR-19a and miR-20a) were frequently increased in NPC tissues compared to the normal tissues. It was also demonstrated that miR-19a was significantly upregulated in NPC C666-1 cells compared to NP69 cells (P<0.01). Knockdown of miR-19a led to a significant decrease in the viability and invasion of NPC C666-1 cells (P<0.01), and induced increased protein expression levels of transforming growth factor β receptor 2 (TGFβR2), which was further identified as a direct target gene of miR-19a by using a luciferase reporter assay. Overexpression of TGFβR2 also suppressed the viability and invasion of C666-1 cells, similar to the effects of miR-19a inhibition. Furthermore, knockdown of TGFβR2 reversed the suppressive effects of miR-19a inhibition on C666-1 cell viability and invasion, suggesting that the role of miR-19a in mediating cell viability and invasion is through directly targeting TGFβR2 in NPC cells. In addition, RT-qPCR data demonstrated that the mRNA expression level of TGFβR2 was markedly reduced in NPC tissues and C666-1 cells. In summary, the present study demonstrated an oncogenic role of miR-19a in NPC via mediation of TGFβR2. Therefore, miR-19a may be a potential therapeutic target for NPC.

microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway

“…Drawn from a previous study, it is concluded that miR-18a is overexpressed in NPC tissues with its association with lymph node metastasis and clinical stage [5]. Besides that, miR-17-92 cluster members including miR-18a are documented to be overexpressed in NPC tissues [25]. Furthermore, upregulated miR-18a is reported to demonstrate in NPC tissues which is connected with tumor node metastasis stage and tumor size [4].…”

MicroRNA-192 promotes the development of nasopharyngeal carcinoma through targeting RB1 and activating PI3K/AKT pathway

“…Many studies have demonstrated that miRNAs take part in the regulation of NPC progression. miR-19a was found to be upregulated and promote development of NPC via targeting TGFβR2 [23]. Similarly, upregulation of miR-192 was also found in esophageal squamous cell carcinoma and squamous cell lung carcinoma [24,25].…”

The Dynamic Roles of TGF-β Signalling in EBV-Associated Cancers

“…It is noteworthy that TGFR-2 expression has been suggested as a positive prognostic marker in DLBCL patients [ 105 ]. Further, the mRNA and/or protein levels of TGFBR1 and TGFBR2 were found to be significantly reduced in primary NPC tissues compared with non-cancerous controls, and their decreased expression correlated with poor survival [ 106 , 107 , 108 , 109 ]. However, a recent report described contradictory results in which TGFR-1 was found to be up-regulated in primary NPC tissues [ 110 ].…”

“…The involvement of cellular miRNAs in the disruption of TGF-β signalling has also been reported. For example, miR-93 and miR-19a, paralogues of the oncogenic miR-17-92 cluster, were shown to promote NPC aggressiveness by down-regulating TGFR-2 [ 108 , 109 ]. Several studies on global miRNA profiling in NPC have identified a number of differentially expressed miRNAs that target the TGF-β pathway [ 114 , 115 , 116 ], but the exact targets within the pathway are yet to be identified.…”