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

Abstract

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.

miR‑208b‑5p inhibits invasion of non‑small cell lung cancer through the STAT3 pathway by targeting interleukin‑9

“…STAT3 is known to be constitutively activated in various types of cancer (9), such as cutaneous melanoma (10), squamous cell carcinoma (11) and oral squamous cell carcinoma (12). In addition to promoting angiogenesis, STAT3 regulates cell proliferation, migration and invasion of tumor cells, indicating its crucial role in the control of tumor growth and metastasis (10,(40)(41)(42). The present study demonstrated that STAT3 inhibitor C188-9 attenuated the expression of EMT-promoting mRNA levels.…”

“…STAT3 transduces signals from the cell membrane receptors to the nucleus, where it acts as a transcription factor. STAT3 is known to be constitutively activated in various types of cancer (9), such as cutaneous melanoma (10), squamous cell carcinoma (11) and oral squamous cell carcinoma (12). In addition to promoting angiogenesis, STAT3 regulates cell proliferation, migration and invasion of tumor cells, indicating its crucial role in the control of tumor growth and metastasis (10,(40)(41)(42).…”

“…Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signals from cell surface receptors to the nucleus (9). Numerous evidences suggest that STAT3 is constitutively activated in various types of cancer and serve a crucial role in tumor growth and metastasis (9)(10)(11)(12). In addition, STAT3 regulates cellular proliferation, invasion, migration and angiogenesis, which are essential for cancer metastasis (13).…”

IL‑22/IL‑22R1 promotes proliferation and collagen synthesis of MRC‑5 cells via the JAK/STAT3 signaling pathway and regulates airway subepithelial fibrosis

“…Subepithelial lung fibroblast proliferation, transformation to myofibroblasts and synthesis of extracellular matrix are the main mechanisms leading to subepithelial fibrosis in patients with asthma (25,26). IL-22 is an immune-related cytokine that was discovered in previous years and plays a role in the occurrence and development of psoriasis, arthritis and cancer (22,27,28). Previously, it was reported that IL-22 promotes allergic airway inflammation in sensitized mice in vivo (17).…”

“…IL-22 has been reported to activate the JAK/STAT3 signaling pathway. Furthermore, STAT3 participates in airway remodeling (22). Therefore, the present study investigated the relationship between airway remodeling and the IL-22/IL-22R1 signaling pathway in bronchial asthma.…”