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A lncRNA, SPRIGHTLY, interacts with Polypyrimidine Tract Binding Protein 1 (PTBP1) and modulates SET And MYND Domain Containing 3 (SMYD3) exon skipping.

ABSTRACT: During the course of surveying Medulloblastoma (MB) group specific lncRNAs, we found that SPRIGHTLY was highly upregulated in group 4 cell lines and patient derived xenografts (PDX). Its knock down reduced cell proliferation, invasion, and colony formation. It binds to the intron region of SMYD3 pre-mRNA and regulates SMYD3 exon 5 skipping together with PTBP1 protein. In group 4 cell line, the increase of SMYD3 affects EGFR pathway and regulates its downstream gene transcription. Inquiring SMYD3 and SMYD3 E5D transcripts expression in the patient RNA-seq data suggests that balancing two transcripts level seems to be associated with tumor development or maintenance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189643 | GEO | 2022/10/31

REPOSITORIES: GEO

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Project description:SET (Su) and MYND (myeloid-Nervy-DEAF-1) domain-containing protein (SMYD) is a methyltransferase family, including five members of which SMYD1, SMYD2, SMYD3 and SMYD4, has been found to play critical roles in human carcinogenesis. It has been demonstrated that the altered expression of SMYD3 is associated with the progression of several solid tumors, including bladder cancer, glioma, gastric cancer, prostate cancer and colorectal cancer. Several trials have explored the effects of SMYD3 overexpression on proliferation, viability, cancer cells migration and invasion. The series of elegant experiments suggested that SMYD3 could serve as a potential biomarker for clinically aggressive disease and an attractive therapeutic target. In our previous study (PMID: 26980013), we found SMYD3 expression is frequently upregulated in human esophageal squamous cell carcinoma (ESCC) clinical tissues, correlating with overall survival of ESCC patients. RNAi-mediated knockdown of SMYD3 suppressed ESCC cell proliferation, migration and invasion in vitro, and inhibited local tumor invasion in vivo. To identify genes and biological pathways associated with SMYD3 functions and mechanism, SMYD3 was knockdowned bypGLV3/H1/GFP/+Puro Vector in ESCC cell line KYSE150 with an empty plasmid as a control, these two cells were applied for mRNA expression profile analyses to find the differentially expressed genes using GeneChipÂ® PrimeViewâ¢ Human Gene Expression Array. shRNA sequences targeting SMYD3 was ligated into the pGLV3/H1/GFP/+Puro Vector and transfected into ESCC cell line KYSE150 with an empty plasmid as a control. The mRNA expression profiles of SMYD3 knockdown was analyzed by GeneChipÂ®Â PrimeViewâ¢Â HumanÂ Gene Expression Array (Affymetrix,Â USA). The knockdown of SMYD3 was confirmed by QRT-PCR and Western blot. Total RNAs from SMYD3 knockdown cells and control cells were extracted for GeneChipÂ® PrimeViewâ¢ Human Gene Expression Array.

Dataset Information

A lncRNA, SPRIGHTLY, interacts with Polypyrimidine Tract Binding Protein 1 (PTBP1) and modulates SET And MYND Domain Containing 3 (SMYD3) exon skipping.

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