Knockdown of COPA, Identified by Loss-of-Function Screen, Induces Apoptosis and Suppresses Tumor Growth in Mesothelioma Mouse Model

Sudo, Hitomi; Tsuji, Atsushi B.; Sugyo, Aya; Kohda, Masakazu; Sogawa, Chizuru; Yoshida, Chisato; Harada, Yoshi Nobu; Hino, Okio; Saga, Tsuneo

doi:10.1016/j.ygeno.2010.02.002

Cited by 60 publications

(57 citation statements)

References 18 publications

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“…S9 in the supplemental material). This apoptotic signature is consistent with the observation that the depletion of eIF4A3 and Y14, respectively, decreases cell growth (63) and promotes apoptosis in mouse mesothelioma cells (69). Depleting other RNA binding proteins that did not modulate Bcl-x splicing did not elicit apoptosis (see Table S1 and Fig.…”

Section: Components More Prevalently Associated With Ejc Function Affsupporting

confidence: 89%

“…(C) Annexin V assay in HeLa cells transfected with siRNAs targeting EJC components. Cells were immunostained for annexin V (red), and nuclei were labeled with Hoechst stain (blue) (69). The percentage of apoptotic cells was quantitated (bottom graph) upon transfection of siRNAs targeting eIF4A3, Y14, and RNPS1 (2 siRNAs each) and compared to that for various controls (Lipofectamine alone, negative-control siRNAs targeting KITLG and cyclin D1, and a positive-control siRNA targeting KIF11 [71]).…”

Section: Discussionmentioning

confidence: 99%

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Proteins Associated with the Exon Junction Complex Also Control the Alternative Splicing of Apoptotic Regulators

Michelle

Cloutier

Toutant

et al. 2012

Molecular and Cellular Biology

120

142

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Several apoptotic regulators, including Bcl-x, are alternatively spliced to produce isoforms with opposite functions. We have used an RNA interference strategy to map the regulatory landscape controlling the expression of the Bcl-x splice variants in human cells. Depleting proteins known as core (Y14 and eIF4A3) or auxiliary (RNPS1, Acinus, and SAP18) components of the exon junction complex (EJC) improved the production of the proapoptotic Bcl-x S splice variant. This effect was not seen when we depleted EJC proteins that typically participate in mRNA export (UAP56, Aly/Ref, and TAP) or that associate with the EJC to enforce nonsense-mediated RNA decay (MNL51, Upf1, Upf2, and Upf3b). Core and auxiliary EJC components modulated Bcl-x splicing through different cis-acting elements, further suggesting that this activity is distinct from the established EJC function. In support of a direct role in splicing control, recombinant eIF4A3, Y14, and Magoh proteins associated preferentially with the endogenous Bcl-x pre-mRNA, interacted with a model Bcl-x pre-mRNA in early splicing complexes, and specifically shifted Bcl-x alternative splicing in nuclear extracts. Finally, the depletion of Y14, eIF4A3, RNPS1, SAP18, and Acinus also encouraged the production of other proapoptotic splice variants, suggesting that EJC-associated components are important regulators of apoptosis acting at the alternative splicing level.

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Section: Components More Prevalently Associated With Ejc Function Affsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Proteins Associated with the Exon Junction Complex Also Control the Alternative Splicing of Apoptotic Regulators

Michelle

Cloutier

Toutant

et al. 2012

Molecular and Cellular Biology

120

142

View full text Add to dashboard Cite

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“…One report has shown that EIF3D is relatively stable and could be a reliable reference gene for assessing gene expression in nasopharyngeal cancer [22]. On the contrary, another study in the same year has reported that EIF3D may be involved in the anti-apoptosis and tumorigenesis of mesothelioma [23]. In the present study, we add a new finding to the function of EIF3D in PCa.…”

Section: Discussionsupporting

confidence: 47%

The oncogenic role of EIF3D is associated with increased cell cycle progression and motility in prostate cancer

et al. 2015

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EIF3 is the largest multi-protein complex, and several studies have revealed the oncogenic roles of its subunits in many human cancers. However, the roles of EIF3D in the development and progression of PCa remain uncovered. In the present study, the expression of EIF3D in prostate cancer and paracarcinoma tissues, as well as PCa cell lines, was examined. In PCa tissues, the expression of EIF3D was up-regulated compared to that in paracarcinoma tissues. In order to investigate whether EIF3D could serve as potential therapeutic target for prostate cancer, EIF3D was knocked down to verify its functional role in prostate cancer cells. After EIF3D knockdown in PC-3 and DU145 cells, cell proliferation, invasion and colony formation were significantly inhibited; meanwhile, cell cycle analysis revealed cell cycle arrest at G2/M phase. EIF3D is associated with PCa, and silencing EIF3D will result in decreased proliferation, and migration, as well as G2/M arrest in DU145 and PC-3 cells. These results suggest that EIF3D plays an oncogenic role in PCa development and progression.

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“…Recently, eIF3d is continually described in cancers. Sudo et al [18] firstly identified eIF3d as one of genes involved in mesothelioma cell viability using a genome-wide small interfering RNA library, suggesting that eIF3d may have the potential of a diagnostic marker and a therapeutic target of mesothelioma. eIF3d, eIF3e, eIF3f, eIF3h and eIF4b have been identified to be up-regulated in gastric cancer patients with acquired resistance to cisplatin and fluorouracil (CF) [19].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of eIF3d inhibits cell proliferation through G2/M phase arrest in non-small cell lung cancer

2015

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Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains the leading cause of cancer-related death worldwide. Eukaryotic translation initiation factor 3, subunit d (eIF3d) has been recognized recently in several human cancers. In this paper, we attempt to evaluate the functional role of eIF3d in NSCLC cells. Lentivirus-mediated RNA interference (RNAi) was applied to silence eIF3d in the human NSCLC cell lines A549 and 95D. Cell viability was measured by MTT. Cell colony-forming ability was measured by colony formation. Cell cycle progression was determined by propidium iodide staining and flow cytometry. Intracellular signaling molecules were detected using a PathScan(®) intracellular signaling array kit. In this study, we firstly proved that lentivirus-mediated RNAi specifically suppressed the expression of eIF3d both at the mRNA and protein levels in A549 and 95D cell lines. Further investigations revealed that eIF3d knockdown significantly inhibited cell proliferation and colony formation. Moreover, the cell cycle of A549 cells was arrested at G2/M phase after eIF3d knockdown. Furthermore, the activations of AKT, HSP27 and SAPK/JNK were suppressed by eIF3d knockdown. This study highlights the crucial role of eIF3d in promoting NSCLC cell proliferation, and provides a foundation for further study into the clinical potential of lentiviral-mediated delivery of eIF3d RNAi therapy for treatment of NSCLC.

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Knockdown of COPA, Identified by Loss-of-Function Screen, Induces Apoptosis and Suppresses Tumor Growth in Mesothelioma Mouse Model

Cited by 60 publications

References 18 publications

Proteins Associated with the Exon Junction Complex Also Control the Alternative Splicing of Apoptotic Regulators

Proteins Associated with the Exon Junction Complex Also Control the Alternative Splicing of Apoptotic Regulators

The oncogenic role of EIF3D is associated with increased cell cycle progression and motility in prostate cancer

Knockdown of eIF3d inhibits cell proliferation through G2/M phase arrest in non-small cell lung cancer

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