Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma

Abstract

Background Melanoma is an extremely aggressive type of skin cancer and experiencing a expeditiously rising mortality in a current year. Exploring new potential prognostic biomarkers and therapeutic targets of melanoma are urgently needed. The ambition of this research was to identify genetic markers and assess prognostic performance of N6-methyladenosine (m6A) regulators in melanoma. Methods Gene expression data and corresponding clinical informations of melanoma patients as well as sequence data of normal controls are collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Quantitative real-time PCR (qRT-PCR) analysis was carried out to detect the RNA expression of IGF2BP3 in A375 cell line, melanoma tissues, and normal tissues. Western blot, cell proliferation, and migration assays were performed to assess the ability of IGF2BP3 in A375 cell line. Results Differently expressed m6A regulators between tumor samples and normal samples were analyzed. A three-gene prognostic signature including IGF2BP3, RBM15B, and METTL16 was constructed, and the risk score of this signature was identified to be an independent prognostic indicator for melanoma. In addition, IGF2BP3 was verified to promote melanoma cell proliferation and migration in vitro and associate with lymph node metastasis in clinical samples. Moreover, risk score and the expression of IGF2BP3 were positively associated with the infiltrating immune cells and these hub genes made excellent potential drug targets in melanoma. Conclusion We identified the genetic changes in m6A regulatory genes and constructed a three-gene risk signature with distinct prognostic value in melanoma. This research provided new insights into the epigenetic understanding of m6A regulators and novel therapeutic strategies in melanoma.

METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m6A-dependent manner

“…Liu et al. reported that METTL16 was associated with poor prognosis of patients with melanoma [ 53 ]. Wang et al.…”

Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential

“…IGF2BP3 might be a pan-cancer oncogene, as its overexpression is associated with poor patient survival in various cancers, including kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, brain lower-grade glioma, and more [ 98 ]. Moreover, IGF2BP3 is upregulated and its high expression conveys tumor progression and worse prognosis in patients with lung adenocarcinoma [ 99 ], esophageal cancer [ 100 ], gastric cancer [ 63 ], pancreatic adenocarcinoma [ 101 ], papillary renal cell carcinoma [ 102 ], colon cancer [ 56 ], clear cell renal cell carcinoma [ 61 ], bladder cancer [ 103 ], prostate cancer [ 104 ], nasopharyngeal carcinoma [ 64 ], laryngeal squamous cell cancer [ 60 ], melanoma [ 105 ], glioma [ 106 ], acute myelocytic leukemia [ 65 ], among others. IGF2BP1 has been identified as an unfavorable prognostic indicator in tumors such as lung adenocarcinoma [ 107 ], endometrial cancer [ 42 ], gastric cancer [ 108 ], hepatocellular carcinoma, and serous ovarian cancer [ 41 ].…”

Research Progress of m6A RNA Methylation in Skin Diseases

“…It was demonstrated that IGF2BP3 promoted proliferation and migration of melanoma cells in vitro. The expression of IGF2BP3 was positively correlated with lymph node metastasis and immune cells infiltrating [ 42 ]. These results provided potential targets of novel drugs for melanoma.…”