miR-181a regulates multiple pathways in hypopharyngeal squamous cell carcinoma

Abstract

MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that play essential roles in a variety of biological processes including apoptosis, proliferation and differentiation. Altered expression of miRNAs in head and neck cancer has been reported, but the consequences of aberrant expression of specific miRNAs on cancer pathways remain vague. Therefore, it is important to identify and elucidate pathways that may be regulated by specific miRNAs in this disease. miR-181a was up-regulated in head and neck versus normal tissues, thus pathway analysis was performed to profile the changes in the activities of ten signaling pathways relevant to cancer influenced by down-regulation of miR-181a. Expression of four pathway reporters were significantly increased (p53/DNA damage, TGFβ, MAPK/ERK and MAPK/JNK), while expression of two pathway reporters were decreased (Wnt and NFkB) upon miR-181a down-regulation. Notch, Myc/Max, hypoxia and cell cycle/pRB-E2F pathways were not significantly affected by miR-181a down-regulation. This study provides insight into the understanding of miRNA regulation on major cancer pathways.

Key words: MicroRNA, head and neck cancer, miR-181a, pathway analysis, luciferase assay, FaDu cell line, transfection, qRT-PCR.