SMAD4-dependent polysome RNA recruitment in human pancreatic cancer cells

Jessica A. Thornley, Heidi W. Trask, Carol S. Ringelberg, Christian J.A. Ridley, Sinny Wang, Richard Cowper Sal-Lari, Jason H. Moore, Murray Korc, Craig R. Tomlinson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Pancreatic cancer is the fourth leading cause of cancer death in the United States because most patients are diagnosed too late in the course of the disease to be treated effectively. Thus, there is a pressing need to more clearly understand how gene expression is regulated in cancer cells and to identify new biomarkers and therapeutic targets. Translational regulation is thought to occur primarily through non-SMAD directed signaling pathways. We tested the hypothesis that SMAD4-dependent signaling does play a role in the regulation of mRNA entry into polysomes and that novel candidate genes in pancreatic cancer could be identified using polysome RNA from the human pancreatic cancer cell line BxPC3 with or without a functional SMAD4 gene. We found that (i) differentially expressed whole cell and cytoplasm RNA levels are both poor predictors of polysome RNA levels; (ii) for a majority of RNAs, differential RNA levels are regulated independently in the nucleus, cytoplasm, and polysomes; (iii) for most of the remaining polysome RNA, levels are regulated via a “tagging” of the RNAs in the nucleus for rapid entry into the polysomes; (iv) a SMAD4-dependent pathway appears to indeed play a role in regulating mRNA entry into polysomes; and (v) a gene list derived from differentially expressed polysome RNA in BxPC3 cells generated new candidate genes and cell pathways potentially related to pancreatic cancer.
Original languageEnglish
Pages (from-to)771-782
JournalMolecular Carcinogenesis
Volume51
Issue number10
DOIs
Publication statusPublished - 1 Oct 2012

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Polyribosomes
Pancreatic Neoplasms
RNA
Genes
Cytoplasm
Messenger RNA
Cause of Death
Neoplasms
Biomarkers
Gene Expression
Cell Line

Cite this

Thornley, J. A., Trask, H. W., Ringelberg, C. S., Ridley, C. J. A., Wang, S., Sal-Lari, R. C., ... Tomlinson, C. R. (2012). SMAD4-dependent polysome RNA recruitment in human pancreatic cancer cells. Molecular Carcinogenesis, 51(10), 771-782. https://doi.org/10.1002/mc.v51.10

SMAD4-dependent polysome RNA recruitment in human pancreatic cancer cells. / Thornley, Jessica A.; Trask, Heidi W.; Ringelberg, Carol S.; Ridley, Christian J.A.; Wang, Sinny; Sal-Lari, Richard Cowper; Moore, Jason H.; Korc, Murray; Tomlinson, Craig R.

In: Molecular Carcinogenesis, Vol. 51, No. 10, 01.10.2012, p. 771-782.

Research output: Contribution to journalArticle

Thornley, JA, Trask, HW, Ringelberg, CS, Ridley, CJA, Wang, S, Sal-Lari, RC, Moore, JH, Korc, M & Tomlinson, CR 2012, 'SMAD4-dependent polysome RNA recruitment in human pancreatic cancer cells', Molecular Carcinogenesis, vol. 51, no. 10, pp. 771-782. https://doi.org/10.1002/mc.v51.10
Thornley JA, Trask HW, Ringelberg CS, Ridley CJA, Wang S, Sal-Lari RC et al. SMAD4-dependent polysome RNA recruitment in human pancreatic cancer cells. Molecular Carcinogenesis. 2012 Oct 1;51(10):771-782. https://doi.org/10.1002/mc.v51.10
Thornley, Jessica A. ; Trask, Heidi W. ; Ringelberg, Carol S. ; Ridley, Christian J.A. ; Wang, Sinny ; Sal-Lari, Richard Cowper ; Moore, Jason H. ; Korc, Murray ; Tomlinson, Craig R. / SMAD4-dependent polysome RNA recruitment in human pancreatic cancer cells. In: Molecular Carcinogenesis. 2012 ; Vol. 51, No. 10. pp. 771-782.
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