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Functional Polymorphism in Pak1-3' Untranslated Region Alters Skin Tumor Susceptibility by Alternative Polyadenylation.
Okumura, Kazuhiro; Saito, Megumi; Isogai, Eriko; Tokunaga, Yurika; Hasegawa, Yoshinori; Araki, Kimi; Wakabayashi, Yuichi.
Affiliation
  • Okumura K; Division of Experimental Animal Research, Cancer Genome Center, Chiba Cancer Center Research Institute, Chiba, Japan.
  • Saito M; Division of Experimental Animal Research, Cancer Genome Center, Chiba Cancer Center Research Institute, Chiba, Japan.
  • Isogai E; Division of Experimental Animal Research, Cancer Genome Center, Chiba Cancer Center Research Institute, Chiba, Japan.
  • Tokunaga Y; Division of Experimental Animal Research, Cancer Genome Center, Chiba Cancer Center Research Institute, Chiba, Japan.
  • Hasegawa Y; Laboratory of Clinical Omics Research, Department of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Japan.
  • Araki K; Division of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
  • Wakabayashi Y; Division of Experimental Animal Research, Cancer Genome Center, Chiba Cancer Center Research Institute, Chiba, Japan. Electronic address: yuichi_wakabayashi@chiba-cc.jp.
J Invest Dermatol ; 142(9): 2323-2333.e12, 2022 09.
Article in En | MEDLINE | ID: mdl-35240107
ABSTRACT
We identified a functional SNP in the 3' untranslated region of Pak1 that is responsible for the skin tumor modifier of MSM 1a locus. Candidate SNPs in the 3' untranslated region of Pak1 from resistance strain MSM/Ms were introduced into susceptible strain FVB/N using CRISPR/Cas9. The 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate skin carcinogenesis experiments revealed an SNP (Pak1-3' untranslated region-6C>T rs31627325) that strongly suppressed skin tumors. Furthermore, MBNL1 bound more strongly to FVB-allele (6C/C) and regulated the transcript length in the 3' untranslated region of Pak1 and tumorigenesis through polyadenylation. Therefore, the alternative polyadenylation of Pak1 is cis-regulated by rs31627325.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Skin Neoplasms / Polyadenylation / P21-Activated Kinases Limits: Animals Language: En Journal: J Invest Dermatol Year: 2022 Document type: Article Affiliation country: Japan
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Skin Neoplasms / Polyadenylation / P21-Activated Kinases Limits: Animals Language: En Journal: J Invest Dermatol Year: 2022 Document type: Article Affiliation country: Japan