Abstract
Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with a genetic predisposition, Epstein-Barr virus infection and chromosomal abnormalities. Recently, several miRNAs have been shown to target specific mRNAs to regulate NPC development and progression. However, the involvement of miRNAs in processes leading to NPC migration and invasion remains to be elucidated. We predicted that miR-29a/b are associated with dysregulated genes controlling NPC through an integrated interaction network of miRNAs and genes. miR-29a/b over-expression in NPC cell lines had no significant effect on proliferation, whereas miR-29b mildly increased the percentage of cells in the G1 phase with a concomitant decrease in the percentage of cells in S phase. Furthermore, we demonstrated that miR-29a/b might be responsible for increasing S18 cell migration and invasion, and only COL3A1 was identified as a direct target of miR-29b despite the fact that both SPARC and COL3A1 were inhibited by miR-29a/b over-expression. Meanwhile, SPARC proteins were increased in metastatic NPC tissue and are involved in NPC progression. Unexpectedly, we identified that miRNA-29b expression was elevated in the serum of NPC patients with a high risk of metastasis. The 5-year actuarial overall survival rates in NPC patients with high serum miR-29b expression was significantly shorter than those with low serum miR-29b expression; therefore, serum miR-29b expression could be a promising prognostic marker.
Highlights
Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignancies of the head and neck in southern China, with a high incidence rate of approximately 10–50/105 individuals per year [1, 2]
The interplay between microRNAs and their target genes contributes to cancer development and progression, and miRNAs are differentially expressed in normal tissues and cancers
Some selected genes were not reposited by BioRGID, aiding to refine the comprehensive interaction network and interrogate the function of proteins encoded by dysregulated genes
Summary
NPC is one of the most prevalent malignancies of the head and neck in southern China, with a high incidence rate of approximately 10–50/105 individuals per year [1, 2]. Certain small noncoding RNAs have recently emerged as master regulators of NPC gene expression by targeting protein-coding mRNAs. miRNAs have been shown to be important gene regulators in many organisms and have already been implicated in a growing number of diseases. MiRNAs of the let-7 family suppress NPC cell proliferation by down-regulating c-Myc expression [4]. Several miRNAs have been shown to target specific mRNAs to regulate NPC development and progression. Those studies did not offer a fully comprehensive view of miRNA-dependent regulation of NPC genes. The predicted targets for the differentially expressed miRNAs are significantly enriched for protein-coding tumor suppressors and oncogenes. The functional significance of miRNA dysregulation may serve to help identify and characterize tumors in human tissues
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