Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells

Chen, Miao; Qian, Long; Borrie, Melinda S.; Sun, Haohui; Zhang, Changlin; Yang, Han; Shi, Dingbo; Gartenberg, Marc R.; Deng, Wuguo

doi:10.1371/journal.pgen.1009899

Cited by 12 publications

(11 citation statements)

References 79 publications

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“…Therefore, it appears that tRNA nuclear export and substrate preferences by Mex67-Mtr2 may be evolutionarily conserved. In contrast, studies in Xenopus oocytes ( 60 ) and human cancer cells ( 59 ) found no role for the Crm1 homologue, Xpo-1, in tRNA nuclear export. Another study identified budding yeast Dbp5, a member of the DEAD box family of proteins, to function in tRNA nuclear export, most probably by collaboration with Mex67 and/or Crm1 ( 61 ).…”

Section: Discussionmentioning

confidence: 85%

“…reported that the Trypanosomatid Mex67 homologue, TbMex67, is involved in the nuclear export of a subset of tRNAs bearing the queuosine modification at position 34 whereas TbMtr2 exported all tested tRNAs ( 33 ) and Chen et al. documented that the Mex67 homologue, NXF1, functions in tRNA nuclear export in human cells ( 59 ). Therefore, it appears that tRNA nuclear export and substrate preferences by Mex67-Mtr2 may be evolutionarily conserved.…”

Section: Discussionmentioning

confidence: 99%

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Three tRNA nuclear exporters in S. cerevisiae: parallel pathways, preferences, and precision

Chatterjee

Marshall

Hopper

2022

Nucleic Acids Research

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tRNAs that are transcribed in the nucleus are exported to the cytoplasm to perform their iterative essential function in translation. However, the complex set of tRNA post-transcriptional processing and subcellular trafficking steps are not completely understood. In particular, proteins involved in tRNA nuclear export remain unknown since the canonical tRNA nuclear exportin, Los1/Exportin-t, is unessential in all tested organisms. We previously reported that budding yeast Mex67-Mtr2, a mRNA nuclear exporter, co-functions with Los1 in tRNA nuclear export. Here we employed in vivo co-purification of tRNAs with endogenously expressed nuclear exporters to document that Crm1 also is a bona fide tRNA nuclear exporter. We document that Los1, Mex67-Mtr2 and Crm1 possess individual tRNA preferences for forming nuclear export complexes with members of the 10 families of intron-containing pre-tRNAs. Remarkably, Mex67-Mtr2, but not Los1 or Crm1, is error-prone, delivering tRNAs to the cytoplasm prior to 5′ leader removal. tRNA retrograde nuclear import functions to monitor the aberrant leader-containing spliced tRNAs, returning them to the nucleus where they are degraded by 3′ to 5′ exonucleases. Overall, our work identifies a new tRNA nuclear exporter, uncovers exporter preferences for specific tRNA families, and documents contribution of tRNA nuclear import to tRNA quality control.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Three tRNA nuclear exporters in S. cerevisiae: parallel pathways, preferences, and precision

Chatterjee

Marshall

Hopper

2022

Nucleic Acids Research

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“…It is also known that tRNA abundance can affect mRNA abundance, so that RNA overexpression in cancer can increase protein synthesis. 23 When the amount of tRNA is reduced, there is nothing to carry the mRNA out to the ribosomes, and accumulation occurs in the cell nucleus. Thus, it is possible that there is a relationship between the expression of CTLA-4 in the epithelial cell nucleus of Warthin's tumor with the presence of gene mutations and further research is needed on this matter.…”

Section: Discussionmentioning

confidence: 99%

Role of cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression in the pathogenesis of Warthin’s tumor growth

Qotrunnada

Indriana

Kosasih³

et al. 2022

Dent. J. (Majalah Kedokt. Gigi)

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Background: One of the benign salivary gland tumors is Warthin’s tumor, which is a benign tumor consisting of a papillary cystic structure covered by a double epithelial layer cells and lymphoid stroma with germinal center. Several cases have reported the Warthin’s tumor transformation into a malignant tumor such as lymphoma that develops from their stromal. Expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) as part of the immune checkpoint when highly expressed leads to a more rapid development or progression of tumors. Purpose: To analyze CTLA-4 expression in Warthin’s tumors associated with the pathogenesis of its growth through an escape mechanism from immune checkpoints and analyze based on CTLA expression whether this marker has the potential to be used as immunotherapy by administering anti CTLA-4. Methods: The tissue sections slides of Warthin’s tumor (n=8) were stained with Hematoxylin Eosin and immunostained with Recombinant Anti-CTLA4 antibody [CAL49] (ab237712). The slide with positive CTLA-4 is shown as staining on the cell membrane and/or cytoplasm. Observations were carried out using Optilab. The result is presented as figures. Results: Tumor cells expressed of CTLA-4 show in cytoplasm and/or cell membranes of the epithelial and stromal components of Warthin’s lymphoid. CTLA-4 is expressed lymphoid stroma, which is associated with inhibition of T cell activity against tumor cells, while the exact mechanism of CTLA-4 expression in epithelial components is not known but is thought to induce tumorigenesis and inhibit apoptosis. Conclusion: CTLA-4 is expressed in epithelial and stromal cells of Warthin’s tumor and this expression indicates that Warthin’s tumor cell growth is through the escape mechanism of the CTLA-4 check point immune. Further research is necessary to investigate whether CTLA-4 expression in lymphoid stroma has relate to their transformation toward a malignant tumor of lymphoma.

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“…The integrity of NE and correct nucleocytoplasmic transport are important for many cellular processes, including genome stability, DNA replication, DNA damage, DNA repair, and cell death (7). Notably, abnormal expression of nucleoporin has been reported to exert a critical impact on the progression of various cancers (8)(9)(10)(11). Nonetheless, the expression pattern and underlining mechanisms of NDC1 in HCC have been rarely known.…”

Section: Introductionmentioning

confidence: 99%

Elevated NDC1 expression predicts poor prognosis and correlates with immunity in hepatocellular carcinoma

Liu¹,

Gu²,

Qiu³

et al. 2023

J Gastrointest Oncol

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Background: NDC1 was identified to be a tumor-promoting factor in non-small cell lung cancer and cervical cancer. However, no report had clarified the relationship between NDC1 and hepatocellular carcinoma (HCC). In this paper, we explored the expression and potential functions of NDC1 in HCC for the first time through the rational application of bioinformatics and relevant basic experiments.Methods: NDC1-related expression profiles and clinical data of HCC patients were collected from The Cancer Genome Atlas (TCGA) database, which were verified via quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Univariate and multivariate Cox regression analyses were used to identify NDC1 as an independent factor for HCC prognosis, and NDC1-related signaling pathways were determined by gene set enrichment analysis (GSEA). Furthermore, we deeply probed the potential links of NDC1 to immunity and immune response. Finally, the bioeffects and underlying mechanisms of ectopic NDC1 overexpression and depletion were determined in HepG2 cells by immunoblotting, flow cytometry, Cell-Counting-Kit-8 (CCK-8), and EDU (5-Ethynyl-2'-deoxyuridine).Results: Up-regulated expression of NDC1 was detected by means of the TCGA database, which was consistent with the results obtained from further qRT-PCR, immunohistochemistry and the CPTAC database. Kaplan-Meier (K-M) survival analysis revealed a worse prognosis in HCC patients with high NDC1 expression. Besides, NDC1 was certified to be closely linked to tumor histologic grade, clinical stage and T stage. Moreover, univariate and multivariate Cox regression analyses defined NDC1 as an independent element for HCC prognosis. NDC1-related signaling pathways, utilizing GSEA analysis, were subsequently found out. What's more, NDC1 expression was detected to be enormously associated with microsatellite instability (MSI), immune cell infiltration, immune checkpoint molecules and immune cell pathways. As for immunotherapy, we discovered that different risk groups tended to have different immune checkpoint inhibitor responses, which indicated crucial implication value of NDC1 for HCC immunotherapy. More interestingly, we observed that the overexpression of NDC1 could promote the migration and invasion of HCC cells.Conclusions: Our article demonstrated that NDC1 might serve as a valuable predictor in the prognosis and immunotherapy of HCC. NDC1 played an oncogenic role in HCC.

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Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells

Cited by 12 publications

References 79 publications

Three tRNA nuclear exporters in S. cerevisiae: parallel pathways, preferences, and precision

Three tRNA nuclear exporters in S. cerevisiae: parallel pathways, preferences, and precision

Role of cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression in the pathogenesis of Warthin’s tumor growth

Elevated NDC1 expression predicts poor prognosis and correlates with immunity in hepatocellular carcinoma

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