MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma

Abstract

MicroRNAs (miRNAs) are a family of small non-coding RNA molecules of about 20 -23 nucleotides in length, which negatively regulate protein-coding genes at post-transcriptional level. Using a stem-loop real-time-PCR method, we quantified the expression levels of 270 human miRNAs in 13 nasopharyngeal carcinoma (NPC) samples and 9 adjacent normal tissues, and identified 35 miRNAs whose expression levels were significantly altered in NPC samples. Several known oncogenic miRNAs, including miR-17-92 cluster and miR-155, are among the miRNAs upregulated in NPC. Tumour suppressive miRNAs, including miR-34 family, miR-143, and miR-145, are significantly downregulated in NPC. To explore the roles of these dysregulated miRNAs in the pathogenesis of NPC, a computational analysis was performed to predict the pathways collectively targeted by the 22 significantly downregulated miRNAs. Several biological pathways that are well characterised in cancer are significantly targeted by the downregulated miRNAs. These pathways include TGF-Wnt pathways, G1-S cell cycle progression, VEGF signalling pathway, apoptosis and survival pathways, and IP3 signalling pathways. Expression levels of several predicted target genes in G1-S progression and VEGF signalling pathways were elevated in NPC tissues and showed inverse correlation with the down-modulated miRNAs. These results indicate that these downregulated miRNAs coordinately regulate several oncogenic pathways in NPC.

Five miRNAs as Novel Diagnostic Biomarker Candidates for Primary Nasopharyngeal Carcinoma

“…In NPC, host-and Epstein-Barr virus (EBV)-encoded miRNAs play key roles in almost all of the steps of epithelial cell carcinogenesis, including epithelialmesenchymal to stem-like transition, cell growth, migration, invasion and tumorigenesis (Chen et al, 2009;Liu et al, 2012;Lo et al, 2012). EBV is detected in all NPC cases regardless of differentiation subtype (Wolf et al, 1975;Raab-Traub et al, 1987).…”

miRNA and nasopharyngeal carcinoma

“…Therefore, the study of signal transduction pathways rather than individual target genes will provide new insight into the biological functions of miRNA. Chen et al [40] recently reported that there are 35 miRNAs whose expression levels are significantly changed in NPC tissue biopsies (11 miRNAs, including miR-196b, miR-138, miR-155, miR-142-3p and miR-18a are upregulated in NPC samples; 24 miRNAs, including miR-204, miR-449a, miR-34c-3p, miR-143 and miR-145 are downregulated in NPC samples). Among the 35 miRNAs, there are four miRNAs (miR-142-3p, miR-196b, miR-138 and miR-155) whose expression levels are significantly upregulated and another four (miR-204, miR-195, miR-187 and miR-143) whose expression levels are significantly downregulated.…”

“…There are five specific pathways targeted by downregulated miRNAs: (1) regulation of the G1/S transition; (2) cross-talk between VEGF (vascular endothelial growth factor) and angiopoietin-1 [41,42] signaling; (3) G-protein(-) mediated regulation of MARK-ERK signaling; (4) TGF (transforming growth factor), WNT [43] and cytoskeletal remodeling; (5) signaling by interaction of membrane-bound ESR1 (estrogen receptor 1) with G-proteins. Among these five pathways, regulation of the G1/S transition and cross-talk between VEGF and angiopoietin-1 signaling are the two most relevant pathways for NPC targeted by miRNAs [40].…”

MicroRNAs: novel factors in clinical diagnosis and prognosis for nasopharyngeal carcinoma

“…Previous reports showed that miRNAs were aberrantly expressed in nasopharyngeal carcinoma compared with normal epithelial tissue, and promoted an aggressive tumour phenotype by changing the expression of their mRNA targets [6][7][8] . For instance, Sengupta et al [6] investigated the expressions of 207 miRNAs in 31 NPCs and 10 normal tissues with miRNA microarrays, and demonstrated the involvement of miR29c in NPC metastasis by regulating mRNAs encoding extracellular matrix proteins.…”

“…For instance, Sengupta et al [6] investigated the expressions of 207 miRNAs in 31 NPCs and 10 normal tissues with miRNA microarrays, and demonstrated the involvement of miR29c in NPC metastasis by regulating mRNAs encoding extracellular matrix proteins. Chen et al [7] studied the expression of 270 human miRNAs in 13 NPC samples in comparison with 9 adjacent normal tissues using a stemloop real-time PCR assay, and found the expressions of 35 miRNAs were significantly altered in NPC, thus inferred that some cancer-related pathways enriched with targets of down-regulated miRNAs. We also demonstrated with microarray that 34 miRNAs were differentially expressed between 8 NPC and 4 normal tissues [8] .…”