Identification of dysregulation of sphingolipids in retinoblastoma using liquid chromatography-mass spectrometry

Retinoblastoma (RB) is a rare ocular cancer seen in children that counts for approximately 3% of all childhood cancers. It is found that mutation in RB1, a tumour Suppressor Gene on chromosome 13 as the cause of malignancy. Retinoblastoma protein is the target for ceramide to cause apoptosis. We stu...

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Published in:	Experimental eye research Vol. 240; p. 109798
Main Authors:	Khade, Omkar Surendra, Sasidharan, Sruthy, Jain, Ankit, Maradani, Bhavani Shankar, Chatterjee, Amit, Gopal, Divya, Ravi Kumar, Ranjith Kumar, Krishnakumar, Subramaniyan, Pandey, Akhilesh, Janakiraman, Narayanan, Elchuri, Sailaja V., Gundimeda, Seetaramanjaneyulu
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-03-2024
Subjects:	Drug resistance Glucosyl ceramide Lipidomics Mass spectrometry Retinoblastoma Sphingolipids Lipidomics Sphingolipids Glucosyl ceramide Retinoblastoma Drug resistance Mass spectrometry
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Summary:	Retinoblastoma (RB) is a rare ocular cancer seen in children that counts for approximately 3% of all childhood cancers. It is found that mutation in RB1, a tumour Suppressor Gene on chromosome 13 as the cause of malignancy. Retinoblastoma protein is the target for ceramide to cause apoptosis. We studied lipidomics of two RB cell lines, one aggressive cell line (NCC–RbC-51) derived from a metastatic site and one non aggressive cell line (WERI-Rb1) in comparison with a control cell line (MIO-M1). Lipid profiles of all the cell lines were studied using high resolution mass spectrometer coupled to high performance liquid chromatography. Data acquired from all the three cell lines in positive mode were analyzed to identify differentially expressed metabolites. Several phospholipids and lysophospholipids were found to be dysregulated. We observed upregulation of hexosyl ceramides, and down regulation of dihydroceramides and higher order sphingoglycolipids hinting at a hindered sphingolipid biosynthesis. The results obtained from liquid chromatography-mass spectrometry are validated by using qPCR and it was observed that genes involved in ceramide biosynthesis pathway are getting down regulated. •Lipidomics of Retinoblastoma.•Dysregulation of sphingolipid pathway.•Dysregulation of glucosyl ceramide in RB.•Metabolic shift between aggressive and non-aggressive cancer cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-4835 1096-0007
DOI:	10.1016/j.exer.2024.109798