IL22 drives cutaneous melanoma cell proliferation, migration and invasion through activation of miR-181/STAT3/AKT...

Cutaneous melanoma (CM) is neoplastic growth of melanocytes with strong potential to proliferate and invade, prone to a fatal disease soon which is beyond surgical clearance. The use of regulator involving in antitumor immune responses has been identified as a potential therapeutic option for CM, but still need fully understood at present. Recently, interleukin 22 (IL22), an immune molecule secreted mostly by CD4⁺ T cells, was reported having functions in a variety of human diseases including encouragement of lung cancer progression, yet, its role in CM is lacking. Here, we first found elevated expression of IL22 in both serum of CM patients and tissues. Up-regulated IL22 significantly promoted cell proliferation, migration and invasion in CM cells deriving from different original culture history. Moreover, in vivo CM model, IL22 treatment caused a significant increase in tumor size. Additionally, we found these effects accompanied by obvious increased miR-181 expression in CM. Importantly, both in vivo and in vitro results revealed that miR-181 downregulation reversed the effects of IL22 on CM cell proliferation, migration, invasion, and CM tumor size as well. Finally, in CM cells deriving from different culture history, we identified STAT3 to be a target gene of miR-181. Higher expression level of IL22 suppressed STAT3 expression, while enhanced expression of p-AKT, p-β-catenin and MMP4; however, down-regulation of miR-181 reversed these situations. Thus, we conclude that IL22 promotes CM progression by driving miR-181/STAT3/AKT axis.