RAB22A overexpression promotes the tumor growth of melanoma

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.

O2-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation

“…It was also observed that transfection with the miR-203 specific inhibitor or culture of cells under an extrinsic hypoxia condition (1% O 2 ) significantly increased the RAB22A transcription. The results were consistent with previous reports 4,26. However, the promoting effects by an extrinsic hypoxic condition (1% O 2 ) on the levels of RAB22A transcription were mitigated by treatment with 3f (Fig.…”

Regulation of RAB22A by mir-193b inhibits breast cancer growth and metastasis mediated by exosomes

“…With increasing malignancy and a poor prognosis, RAB22A is highly expressed in various types of cancer. For instance, Su et al demonstrated that the upregulation of RAB22A promoted melanoma cell growth (29). Proliferative effects can be observed from gastric and colorectal cancer cells via the silencing miR-204-5p expression which also targets RAB22A (30,31).…”

Rab22a is a novel prognostic marker for cell progression in breast cancer

“…A further study performed by Qi et al (33) identified that the transmembrane protein, YIPY2, promotes cd147-medated malignant phenotypes by recruiting and activating Rab5 and Rab22a in hepatocellular carcinoma. Su et al (17) found that the increased expression of Rab22a is related to an advanced clinical stage in melanoma and shorter OS. The present study suggests that Rab22a may act as a novel oncogene in Bc and may be a potential therapeutic target.…”

“…The staining intensity as well as positive staining percentage of tumor cells were used for evaluation. The intensity of staining was categorized as previously described (17): 0 (stainless), 1 (light yellow), 2 (yellow brown) and 3 (brown). The proportion of positive staining tumor cells were 0 (0%), 1 (1-10%), 2 (11-25%), 3 (25-50%) and 4 (>50%).…”