Loss of the eukaryotic initiation factor 3f in pancreatic cancer

Doldan, Adriana; Chandramouli, Anupama; Shanas, Reneé; Bhattacharyya, Achyut K.; Cunningham, J. T.; Nelson, Mark A.; Shi, Jiaqi

doi:10.1002/mc.20379

Cited by 58 publications

(69 citation statements)

References 39 publications

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“…Expression in our positive control tissue eliminated the possibility of poor antibody efficacy or influence of other preanalytic factors. Nevertheless, there is immunohistochemical evidence that eIF3 expression is decreased in pancreatic cancer (24,41). Further evidence from cancer profiling arrays shows general downregulation of eIF3 in human tumors (24), which may explain its lack of expression.…”

Section: Discussionmentioning

confidence: 99%

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Humphries

Rajan

Droop

et al. 2017

Clinical Cancer Research

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Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n ¼ 477, training; n ¼ 220, validation set) and quantified in pre-and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P ¼ 0.013; HR ¼ 1.77, 1.12-2.8 and P ¼ 0.035; HR ¼ 1.68, 1.03-2.74, respectively), or when coexpressed (P ¼ 0.01; HR ¼ 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P ¼ 0.016; HR ¼ 2.38 (1.18-4.8), eIF5 P ¼ 0.022; HR ¼ 2.55 (1.14-5.7); coexpression P ¼ 0.001; HR ¼ 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival.Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required.

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Section: Discussionmentioning

confidence: 99%

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Humphries

Rajan

Droop

et al. 2017

Clinical Cancer Research

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“…This result strongly suggests that the activity of the fragment involves the contribution of the WT protein. The knockdown of eIF3f in WT cells was associated with a slight increase (Ϸ30%) in HIV-1 expression, although it is not clear whether this is specific for HIV or rather is due to an overall increase in translation efficiency, on the concept that eIF3f might be a negative regulator of translation (18).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of HIV-1 replication by eIF3f

Valente

Gilmartin²,

Mott³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Viruses often use host machinery in unusual ways to execute different steps during their replication. To identify host factors critical for virus replication, we screened cDNA expression libraries for genes or gene fragments that could interfere with HIV-1 vector transduction. The DNA clone that most potently inhibited HIV-1 expression encoded the N-terminal 91 aa of the eukaryotic initiation factor 3 subunit f (N91-eIF3f). Overexpression of N91-eIF3f or full-length eIF3f drastically restricted HIV-1 replication by reducing nuclear and cytoplasmic viral mRNA levels. N91-eIF3f and eIF3f specifically targeted the 3 long terminal repeat (3LTR) region in the viral mRNA. We show that the 3 end cleavage of HIV-1 mRNA precursors is specifically reduced in N91-eIF3f expressing cells. Our results suggest a role of eIF3f in mRNA maturation and that it can specifically interfere with the 3 end processing of HIV-1 mRNAs.cDNA genetic screen ͉ HIV-1 restriction ͉ RNA maturation ͉ translation factor

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“…Staining for EP4 receptor protein expression on formalin fixed paraffin embedded colon cancer specimens was performed by methods previously described. 31 The intensity of the immunohistochemical signals in each core is graded as (0) negative, (1) weak, (2) moderate, or (3) strong. The proportion of cells staining positively is also evaluated as a percentage.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 receptor in colon cancers

Chandramouli

Onyeagucha

Mercado-Pimentel

et al. 2012

Cancer Biology & Therapy

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These authors contributed equally to this work.Keywords: colorectal cancer, EP4, miR-101, post-transcriptional regulation Purpose: Expression of the PGE2 receptor, EP4, is up-regulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 receptor is not known. The present study was conducted to investigate the regulation of EP4 receptor by miRNAs.Experimental Design: We analyzed 26 colon cancers (i.e. 15 adenocarcinomas and 9 adenomas) and 16 normal colon specimens for EP4 receptor expression by immunohistochemistry. A bioinformatics approached identified putative microRNA binding sites with the 3'-UTR of the EP4 receptor. Both colon cancer cell lines and tumor specimens were analyzed for miR-101 and EP4 expression by qRT-PCR and Western analysis respectively and simultaneously in situ hybridizations was used to confirm our results. In vitro and in vivo assays were used to confirm our clinical findings.Results: We observed an inverse correlation between the levels of miR-101 and EP4 receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase reporter containing the EP4 receptor-3'-UTR. In contrast, a mutant EP4 receptor-3'-UTR construct was unaffected. Ectopic expression of miR-101 markedly reduced cell proliferation and motility. Co-transfection of EP4 receptor could rescue colon cancer cells from the tumor suppressive effects of miR-101. Moreover, the pharmacologic inhibition of EP4 receptor signaling or silencing of EP4 receptor phenocopied the effect of miR-101. This is the first study to show that the EP4 receptor is negatively regulated by miR-101.Conclusions: These data provide new insights in the modulation of EP-4 receptor expression at the post-transcriptional level by miR-101 and suggests therapeutic strategies against miR-101 targets may be warranted.

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Loss of the eukaryotic initiation factor 3f in pancreatic cancer

Cited by 58 publications

References 39 publications

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Inhibition of HIV-1 replication by eIF3f

MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 receptor in colon cancers

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