Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer

Figure 1 SET and MYND domain-containing protein 2 gene expression in cancer. A: The gene expression profiles of SET and MYND domain-containing protein 2 (SMYD2) across 31 types of tumor samples and paired normal tissues from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project, the analysis was performed using the Gene Expression Profiling Interactive Analysis (GEPIA2); B: Differences in SMYD2 expression between pancreatic ductal adenocarcinoma tissues and paired normal tissues. TPM: Transcripts per kilobase of exon per million mapped reads; ACC: Adrenocortical carcinoma; BLCA: Bladder urothelial carcinoma; BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; DLBC: Lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and neck squamous cell carcinoma; KICH: Kidney chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute myeloid leukemia; LGG: Lower grade glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; OV: Ovarian serous cystadenocarcinoma; PAAD/PDAC: Pancreatic ductal adenocarcinoma; PCPG: Pheochromocytoma and paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin cutaneous melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular germ cell tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine corpus endometrial carcinoma; UCS: Uterine carcinosarcoma; n: Number of samples. ^aP < 0.001 is indicated by three asterisks.

Figure 2 A schematic model for SET and MYND domain-containing protein 2 driving pancreatic cancer development via methylation of nonhistone proteins. SET and MYND domain-containing protein 2 (SMYD2) can methylate several nonhistone proteins that may be involved in pancreatic cancer tumorigenesis, including p53, PTEN, retinoblastomaassociated protein (RB), and mitogen-activated protein kinase activated protein kinase 3 (MAPKAPK3). SMYD2 methylates and inactivates p53 to promote cell proliferation. PTEN is downregulated by SMYD2-mediated methylation, which promotes cell proliferation through activation of PI3K signaling. Methylation of RB by SMYD2 enhances RB phosphorylation, which allows E2F to disassociate from the RB-E2F complex and enhances E2F activity to promote cell cycle progression. SMYD2 impacts the RTK/Ras pathway through methylation of MAPKAPK3 to promote cell growth. MAPKAPK3: Mitogen-activated protein kinase activated protein kinase 3; RB: Retinoblastoma-associated protein.