MicroRNA Profiling and Target Genes Related to Metastasis of Salivary Adenoid Cystic Carcinoma

Abstract

Background/aim: Perineural invasion and distant metastasis lead to a poor prognosis of adenoid cystic carcinoma and there is no effective therapy available. MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression, which can be biomarkers or therapeutic targets for certain cancer types. We aimed to identify miRNAs and their target genes possibly involved in metastasis of salivary gland adenoid cystic carcinoma (SACC).

Materials and methods: Using Nanostring nCounter analysis, we examined miRNA expression in two SACC cell lines: SACC-83 and SACC-LM, with low and high lung metastasis rates, respectively. We then verified the differentially expressed miRNAs with real-time polymerase chain reaction in the cell lines and in tumor samples from patients with SACC. miRNA target-gene expression was also analyzed.

Results: SACC-83 showed higher gene expression of miR-130a, miR-342, and miR-205; SACC-LM showed higher gene expression of miR-99a and miR-155. In human tissue, miR-205 was highly expressed in the primary SACC, while miR-155 and miR-342 were highly expressed in recurrent SACC. Six predicted target genes of miRNA-155 and miR-99a linked to tumorigenesis were further analyzed and RNA expression of ubiquitin-like modifier activating enzyme 2 (UBA2) was higher in SACC than normal salivary gland tissue, and higher in primary compared to recurrent SACC (p<0.05). RNA expression of retinoic acid receptors (RARS) was higher in tissue from primary than recurrent SACC and normal salivary gland (p<0.05), but that in recurrent SACC was not significantly higher than normal salivary gland tissue. RNA expression of minichromosome maintenance 8 homologous recombination repair factor (MCM8) and 24-dehydrocholesterol reductase (DHCR24) was higher in primary SACC than normal salivary gland tissue (p<0.05).

Conclusion: miR-99a, miR-155, miR-130a, miR-342, and miR-205 may play a role in metastasis of SACC. MiR-155 may be involved in SACC metastasis through UBA2 pathways, and UBA2 may function as a biomarker/mediator of SACC metastasis.

Keywords: MicroRNA; metastasis; perineural invasion; recurrence; salivary adenoid cystic carcinoma.