The crucial roles of m^(6)A RNA modifications in cutaneous cancers:Implications in pathogenesis,metastasis,drug resistance,and targeted therapies

N6-methyladenosine(m^(6)A)is the most abundant internal modification on RNA.It is a dynamical and reversible process,which is regulated by m^(6)A methyltransferase and m^(6)A demethylase.The m^(6)A modified RNA can be specifically recognized by the m^(6)A reader,leading to RNA splicing,maturation,degradation or translation.The abnormality of m^(6)A RNA modification is closely related to a variety of biological processes,especially the occurrence and development of tumors.Recent studies have shown that m^(6)A RNA modification is involved in the pathogenesis of skin cancers.However,the precise molecular mechanisms of m^(6)A-mediated cutaneous tumorigenesis have not been fully elucidated.Therefore,this review will summarize the biological characteristics of m^(6)A modification,its regulatory role and mechanism in skin cancers,and the recent research progress of m^(6)A-related molecular drugs,aiming to provide new ideas for clinical diagnosis and targeted therapy of cutaneous cancers.

Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis:A Systematic Review

Psoriasis （Ps） and psoriatic arthritis （PsA） are genetically complex diseases with strong genetic evidence. Recently, susceptibility genes for Ps and PsA have been identified within the late cornified envelop （LCE） gene cluster, especially the cluster 3 （LCE3） genes. It is noteworthy that the deletion of LCE3B and LCE3C （LCE3C_LCE3B-del） is significantly associated with these two diseases. Gene-gene interactions between LCE3 genes and other genes are associated with Ps and PsA. LCE3 genes also have pleiotropic effect on some autoimmune diseases, such as rheumatoid arthritis, atopic dermatitis and systemic lupus erythematosus. Further studies need to focus on the potential function of LCE3 genes in the pathogenesis of Ps and PsA in the future.

A rare variant in COL11A1 is strongly associated with adult height in Chinese Han population

Human height is a highly heritable trait in which multiple genes are involved. Recent genome-wide association studies （GWASs） have identified that COL11A1 is an important susceptibility gene for hu- man height. To determine whether the variants of COL11A 1 are associated with adult and children height, we analyzed splicing and coding single-nucleotide variants across COL11A1 through exome-targeted sequencing and two validation stages with a total 20,426 Chinese Han samples. A total of 105 variants were identified by exome-targeted sequencing, of which 30 SNPs were located in coding region. The strongest association signal was chrl 103380393 with P value of 4.8 × 10-7. Chrl_103380393 also showed nominal significance in the validation stage （P = 1.21×10 6）. Combined analysis of 16,738 samples strengthened the original association of chrl 103380393 with adult height （Pcombinea - 3.1×10 8）, with an increased height of 0.292sd （standard deviation） per G allele （95% CI： 0.19-0.40）. There was no evidence （P = 0.843） showing that chrl 103380393 altered child height in 3688 child samples. Only the group of 12-15 years showed slight significance with P value of 0.0258. This study firstly shows that genetic variants of COL11A1 contribute to adult height in Chinese Han population but not to children height, which expand our knowledge of the genetic factors underlying height variation and the biological regulation of human height.