Abstract
Malignant melanoma is the most aggressive type of skin cancer. RAB22A, a member of RAS oncogene family, has been found to be significantly upregulated in multiple human cancers. In the present study, we found that RAB22A mRNA expression was significantly upregulated in melanoma tissues (including 60 primary melanomas and 84 metastatic melanomas) compared to benign nevi (n = 20), which were significantly higher in metastatic melanoma tissues than primary tissues. Immunohistochemistry data further showed that the positive immunoreactivity of RAB22A was detected in 66% (95/144) melanoma tissues, but not in benign nevi. Moreover, high expression of RAB22A was significantly associated with advanced clinical stage in melanoma. Furthermore, patients with high RAB22A expression had shorter overall survival compared those with low expression of RAB22A. In-vitro study showed that RAB22A was also upregulated in melanoma cell lines WM35, A375, WM451, and SK-MEL-1, when compared with the normal melanocyte HM cells. Knockdown of RAB22A significantly reduced the proliferation, migration and invasion of melanoma A375 cells, while overexpression of RAB22A significantly promoted these malignant phenotypes. In addition, RAB22A was found to be a target of miR-203, a tumor suppressive miRNA in melanoma. Besides, miR-203 was downregulated in melanoma tissues and cell lines, when compared with benign nevi and HM cells, respectively. Taken these findings together, our study could validate an oncogenic role of RAB22A in melanoma, suggesting that RAB22A may be a potential therapeutic target for melanoma.
Highlights
Malignant melanoma is one of the most aggressive forms of skin cancer in worldwide, with a very poor 5-year survival rate [1]
We found that RAB22A mRNA expression was significantly upregulated in melanoma tissues compared to benign nevi (n = 20), which were significantly higher in metastatic melanoma tissues than primary tissues
High expression of RAB22A was significantly associated with advanced clinical stage in melanoma (P < 0.05), but not with age, sex, family history, ulcer, or occurrence site. These findings suggest that upregulation of RAB22A may contribute to the malignant progression of melanoma
Summary
Malignant melanoma is one of the most aggressive forms of skin cancer in worldwide, with a very poor 5-year survival rate [1]. Significant progresses have been made in the early diagnosis and treatment of this disease, the prognosis of melanoma remains poor, mainly due to its recurrence and metastasis as well as lack of efficient biomarkers [3]. Many oncogenes and tumor suppressor genes have been proved to be deregulated in melanoma, which contribute to its malignant progression [4,5,6,7,8]. RAB22A was found to be frequently upregulated in several human cancers and act as an oncogene [12, 13].
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