Integration Analysis of m6A Related Genes in Skin Cutaneous Melanoma and the Biological Function Research of the SPRR1B

Abstract

Melanoma has gradually entered the public view because of its high morbidity and rising prevalence rate, which is a serious threat to human life and health. Recently, N6-methyladenine (m6A) modification has been increasingly confirmed as a potential role in the development of tumogenesis. The purpose of this study is to explore the role and function of m6a-related regulators in the development of melanoma disease at the molecular, cellular and clinical levels through bioinformatics and traditional experiments. We screened and validated differential expression genes (DEGs) in m6A regulators via the GEO, GTEx, TCGA database. The biological processes and signaling pathway involved by DEGs were improved by constructing bioinformational methods such as PPI, GO enrichment, KEGG enrichment, GSEA enrichment, and immune infiltration analysis. And then, we explored the biological function of the key gene, SPRR1B, through cell invasion, migration, infiltration, and tissue chips. The gene IGF2BP3 which was differentially expressed in m6A regulatory factor gene was screened. The results of the enrichment analysis are significantly enriched in the biological processes and pathways of the skin barrier, epidermal differentiation, cytoskeleton, lymphocyte migration and other pathways, pointing to the direction of tumor immunity and tumor metastasis. Tumor immune-related genes YTHDC1, YTHDC2 and ALKBH5 were found. Knock SPRR1B reduction group had a significantly lower invasive ability, the ability to migrate. Nomogram prediction model shows that SPRR1B increased, expressing a worse prognosis. For this purpose, the relationship between m6A regulatory factor and melanoma progression was explored. At the same time, it was found that the abnormal up-regulated expression of SPRR1B before metastasis would lead to poor prognosis of melanoma. SPRR1B promotes the proliferation, invasion and migration of human melanoma cells.

The promotive role of lncRNA MIR205HG in proliferation, invasion, and migration of melanoma cells via the JMJD2C/ALKBH5 axis

“…The rescue experiments based on pcDNA3.1-ALKBH5 and si-MIR205HG-1 disclosed that ALKBH5 overexpression reversed the inhibitory role of silencing MIR205HG-1 in proliferation, invasion, and migration of melanoma cells. In favor of our results, previous investigation has uncovered that ALKBH5 expedites the growth and metastasis of melanoma cells via m 6 A demethylation of forkhead box M1 [19], and confers anti-tumor immunity for melanoma cells [44]. Thereafter, we established the xenograft mouse model and found that MIR205HG downregulation suppressed tumor growth and reduced the positive rate of Ki67, together with reductions in JMJD2C and ALKBH5 levels in tumors.…”

Long Noncoding RNA HAGLROS Promotes the Malignant Progression of Bladder Cancer by Regulating the miR-330-5p/SPRR1B Axis

“…SPRR1B is a member of the SPRR family. Related studies have revealed that the SPRR1B is closely associated with the tumorigenesis and progression of carcinoma by regulating the epithelial-mesenchymal transition (EMT) and participating in the Ras/MEKK1/MKK1 and MAPK signalling pathways ( 29 – 33 ). These above research indicate the direction for further study of the mechanism of SPRR1B in BC.…”

The role of cuproptosis-related gene in the classification and prognosis of melanoma

“…Therefore, a large body of literature has explored the prognosis and metastasis of melanoma. At present, the literature has predicted the prognosis of melanoma patients based on the expression levels of pyroptotic genes, tumor microenvironment status, or m6a-regulated methylation patterns ( 23 – 30 ). Although many bioinformatics studies are predictingognosis of melanoma, the existing cuproptosis-related melanoma research is not abundant.…”