Chanukuppa, V. and Paul, D. and Taunk, K. and Chatterjee, T. and Sharma, S. and Kumar, S. and Santra, M.K. and Rapole, S. (2019) XPO1 is a critical player for bortezomib resistance in multiplemyeloma: A quantitative proteomic approach. Journal of Proteomics, 209. p. 103504.

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Abstract

Among the blood cancers, 13% mortality is caused by Multiple myeloma (MM) type of hematological malignancy. In spite of therapeutic advances in chemotherapy treatment, still MM remains an incurable disease is mainly due to emergence of chemoresistance. At present time, FDA approved bortezomib is the first line drug for MM treatment. However, like other chemotherapy, MM patients are acquiring resistance against bortezomib. The present study aims to identify and validate bortezomib resistant protein targets in MM using iTRAQ and label free quantitative proteomic approaches. 112 differentially expressed proteins were commonly found in both approaches with similar differential expression pattern. Exportin-1 (XPO1) protein was selected for further validation as its significant high expression was observed in both iTRAQ and label free analysis. Bioinformatic analysis of these common differentially expressed proteins showed a clear cluster of proteins such as SMC1A, RCC2, CSE1, NUP88, NUP50, TPR, HSPA14, DYNLL1, RAD21 and RANBP2 being associated with XPO1. Functional studies like cell count assay, flow cytometry assay and soft agar assay proved that XPO1 knock down in RPMI 8226R cell line results in re-sensitization to bortezomib drug. The mass spectrometry data are available via ProteomeXchange with identifier

Item Type:	Article
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	21 Feb 2020 09:56
Last Modified:	21 Feb 2020 09:56
URI:	http://nccs.sciencecentral.in/id/eprint/747

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