title: Heterogeneous nuclear ribonucleoproteins and their interactors are a major class of deregulated proteins in anaplastic astrocytoma: a grade III malignant glioma.
abstract: Anaplastic astrocytoma is a high grade malignant glioma (WHO grade III) of the central nervous system which arises from a low grade II tumor and invariably progresses into lethal glioblastoma (WHO grade IV). We have studied differentially expressed proteins from the microsomal fraction of the clinical specimens of these tumors, using iTRAQ and high-resolution mass spectrometry followed by immunohistochemistry for representative proteins on tissue sections. A total of 2642 proteins were identified, 266 of them with minimum 2 peptide signatures and 2-fold change in expression. The major groups of proteins revealed to be differentially expressed were associated with key cellular processes such as post transcriptional processing, protein translation, and acute phase response signaling. A distinct inclusion among these important proteins is 10 heterogeneous nuclear ribonucleoproteins (hnRNPs) and their interacting partners which have regulatory functions in the cell. hnRNP-mediated post transcriptional events are known to play a major role in mRNA processing, stability, and distribution. Their altered levels have also been observed by us in lower (diffused astrocytoma) and higher (glioblastoma) grades of gliomas, and membrane localization of hnRNPs has also been documented in the literature. hnRNPs may thus be major factors underlying global gene expression changes observed in glial tumors while their differential presence in the microsomal fraction suggests yet additional and unknown roles in tumorigenesis.
authors.affiliation: Centre for Cellular and Molecular Biology-CSIR, Hyderabad, India.
authors.forename: Ravindra Varma
authors.initials: RV
authors.lastname: Polisetty
authors.forename: Poonam
authors.initials: P
authors.lastname: Gautam
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Gupta
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sharma
authors.forename: Megha S
authors.initials: MS
authors.lastname: Uppin
authors.forename: Sundaram
authors.initials: S
authors.lastname: Challa
authors.forename: Praveen
authors.initials: P
authors.lastname: Ankathi
authors.forename: Aniruddh K
authors.initials: AK
authors.lastname: Purohit
authors.forename: Durairaj
authors.initials: D
authors.lastname: Renu
authors.forename: H C
authors.initials: HC
authors.lastname: Harsha
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.forename: Ravi
authors.initials: R
authors.lastname: Sirdeshmukh
mesh_terms: D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000302:isolation & purification* / Q000378:metabolism; D006801:Humans; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009363:Neoplasm Proteins