The dichotomy of NSD1 as an autophagic regulator in HNSCC
Session Number
Project ID: MEDH 16
Advisor(s)
Iuliia Topchu; Northwestern University, Feinberg School of Medicine
Dr. Yanis Boumber; Northwestern University, Feinberg School of Medicine
Discipline
Medical and Health Sciences
Start Date
19-4-2023 10:05 AM
End Date
19-4-2023 10:20 AM
Abstract
Head and Neck Squamous Cell Carcinomas (HNSCCs) classify a diverse family of cancers that constitute the sixth most common type of human cancer in the world, with approximately 900,000 new cases annually. Current HNSCC treatments are highly toxic and carry significant side effects, so it is imperative we explore less invasive potential future drug targets. Nuclear-binding SET Domain 1 (NSD1) is a histone methyltransferase that, along with its paralogs NSD2 and NSD3, catalyzes lysine 36 dimethylation at histone H3 to maintain chromatin structure and regulate transcription. NSD1 mutations are present in 10-13% of HNSCCs and define a favorable prognostic subset of laryngeal HNSCCs. To investigate downstream/upstream signaling upon NSD1 depletion, we performed proteomic analysis (RPPA) and RNA sequencing of HNSCC cell lines Cal27 (tongue) and JHU 011 (laryngeal) with and without NSD1 depletion. RPPA data demonstrated autophagy-regulated gene ULK1 downregulation in both cell lines. RNA sequencing data nominated the upregulation of autophagic genes E2F2, ATG16L1, ATG9a, SRPX, and SQSTM1. To validate these results, we investigated Cal27, JHU011, and JHU 022 cell lines, transfected with control or NSD1 shRNA, by performing RT-QPCR analysis. Our results demonstrated upregulation of these genes upon NSD1 depletion and ULK1 gene downregulation; thus, we can conclude that NSD1 has a dual role as an autophagic gene regulator in HNSCCs.
The dichotomy of NSD1 as an autophagic regulator in HNSCC
Head and Neck Squamous Cell Carcinomas (HNSCCs) classify a diverse family of cancers that constitute the sixth most common type of human cancer in the world, with approximately 900,000 new cases annually. Current HNSCC treatments are highly toxic and carry significant side effects, so it is imperative we explore less invasive potential future drug targets. Nuclear-binding SET Domain 1 (NSD1) is a histone methyltransferase that, along with its paralogs NSD2 and NSD3, catalyzes lysine 36 dimethylation at histone H3 to maintain chromatin structure and regulate transcription. NSD1 mutations are present in 10-13% of HNSCCs and define a favorable prognostic subset of laryngeal HNSCCs. To investigate downstream/upstream signaling upon NSD1 depletion, we performed proteomic analysis (RPPA) and RNA sequencing of HNSCC cell lines Cal27 (tongue) and JHU 011 (laryngeal) with and without NSD1 depletion. RPPA data demonstrated autophagy-regulated gene ULK1 downregulation in both cell lines. RNA sequencing data nominated the upregulation of autophagic genes E2F2, ATG16L1, ATG9a, SRPX, and SQSTM1. To validate these results, we investigated Cal27, JHU011, and JHU 022 cell lines, transfected with control or NSD1 shRNA, by performing RT-QPCR analysis. Our results demonstrated upregulation of these genes upon NSD1 depletion and ULK1 gene downregulation; thus, we can conclude that NSD1 has a dual role as an autophagic gene regulator in HNSCCs.