TY - JOUR
T1 - SFPQ promotes an oncogenic transcriptomic state in melanoma
AU - Bi, O.
AU - Anene, C. A.
AU - Nsengimana, J.
AU - Shelton, M.
AU - Roberts, W.
AU - Newton-Bishop, J.
AU - Boyne, J. R.
N1 - Funding Information:
The authors would like to thank Dr. M.J. Thornton and Dr. S. Sikkink for assistance with primary melanocyte cell culture and Prof. M. Dickman for providing the pSFPQ-FLAG construct. This work was funded by a personal scholarship to OB by Mr. Shaukat Ali, British Skin Foundation award to JRB (030/s/18) and MRC award MR/M019012/1 to JNB.
Publisher Copyright:
© 2021, Crown.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/19
Y1 - 2021/8/19
N2 - The multifunctional protein, splicing factor, proline- and glutamine-rich (SFPQ) has been implicated in numerous cancers often due to interaction with coding and non-coding RNAs, however, its role in melanoma remains unclear. We report that knockdown of SFPQ expression in melanoma cells decelerates several cancer-associated cell phenotypes, including cell growth, migration, epithelial to mesenchymal transition, apoptosis, and glycolysis. RIP-seq analysis revealed that the SFPQ-RNA interactome is reprogrammed in melanoma cells and specifically enriched with key melanoma-associated coding and long non-coding transcripts, including SOX10, AMIGO2 and LINC00511 and in most cases SFPQ is required for the efficient expression of these genes. Functional analysis of two SFPQ-enriched lncRNA, LINC00511 and LINC01234, demonstrated that these genes independently contribute to the melanoma phenotype and a more detailed analysis of LINC00511 indicated that this occurs in part via modulation of the miR-625-5p/PKM2 axis. Importantly, analysis of a large clinical cohort revealed that elevated expression of SFPQ in primary melanoma tumours may have utility as a prognostic biomarker. Together, these data suggest that SFPQ is an important driver of melanoma, likely due to SFPQ–RNA interactions promoting the expression of numerous oncogenic transcripts.
AB - The multifunctional protein, splicing factor, proline- and glutamine-rich (SFPQ) has been implicated in numerous cancers often due to interaction with coding and non-coding RNAs, however, its role in melanoma remains unclear. We report that knockdown of SFPQ expression in melanoma cells decelerates several cancer-associated cell phenotypes, including cell growth, migration, epithelial to mesenchymal transition, apoptosis, and glycolysis. RIP-seq analysis revealed that the SFPQ-RNA interactome is reprogrammed in melanoma cells and specifically enriched with key melanoma-associated coding and long non-coding transcripts, including SOX10, AMIGO2 and LINC00511 and in most cases SFPQ is required for the efficient expression of these genes. Functional analysis of two SFPQ-enriched lncRNA, LINC00511 and LINC01234, demonstrated that these genes independently contribute to the melanoma phenotype and a more detailed analysis of LINC00511 indicated that this occurs in part via modulation of the miR-625-5p/PKM2 axis. Importantly, analysis of a large clinical cohort revealed that elevated expression of SFPQ in primary melanoma tumours may have utility as a prognostic biomarker. Together, these data suggest that SFPQ is an important driver of melanoma, likely due to SFPQ–RNA interactions promoting the expression of numerous oncogenic transcripts.
KW - clinical genetics
KW - skin cancer
UR - http://www.scopus.com/inward/record.url?scp=85109328501&partnerID=8YFLogxK
U2 - 10.1038/s41388-021-01912-4
DO - 10.1038/s41388-021-01912-4
M3 - Article
C2 - 34218270
AN - SCOPUS:85109328501
VL - 40
SP - 5192
EP - 5203
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 33
ER -
