Nonsense‐mediated decay factor SMG7 sensitizes cells to TNFα‐induced apoptosis via CYLD tumor suppressor and the noncoding oncogene <i>Pvt1</i>

Yang, Limeng; Kraft, Vanessa A N; Pfeiffer, Susanne; Merl-Pham, Juliane; Bao, Xuanwen; An, Yu; Hauck, Stefanie M.; Schick, Joel

doi:10.1002/1878-0261.12754

Cited by 8 publications

(5 citation statements)

References 59 publications

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“…NMD regulates NF-kB also at different levels and SMG7 was identified as a determinant of resistance to TNF-induced extrinsic apoptosis induction [59]. Accordingly, its depletion was shown to prevent sensitivity to TNF and favor activation of the NF-kB pathway via reduction of tumor suppressor cylindromatosis CYLD [60], a deubiquitinase that cleaves polyubiquitin chains and is involved in TNF-induced necroptosis.…”

Section: Nmd As a Tumor Suppressor Interconnected With The Tumor Microenvironment (Tme)mentioning

confidence: 99%

Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy

Bongiorno

Colombo

Lecis

2021

J Exp Clin Cancer Res

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Nonsense-mediated mRNA decay (NMD) is a highly conserved cellular surveillance mechanism, commonly studied for its role in mRNA quality control because of its capacity of degrading mutated mRNAs that would produce truncated proteins. However, recent studies have proven that NMD hides more complex tasks involved in a plethora of cellular activities. Indeed, it can control the stability of mutated as well as non-mutated transcripts, tuning transcriptome regulation. NMD not only displays a pivotal role in cell physiology but also in a number of genetic diseases. In cancer, the activity of this pathway is extremely complex and it is endowed with both pro-tumor and tumor suppressor functions, likely depending on the genetic context and tumor microenvironment. NMD inhibition has been tested in pre-clinical studies showing favored production of neoantigens by cancer cells, which can stimulate the triggering of an anti-tumor immune response. At the same time, NMD inhibition could result in a pro-tumor effect, increasing cancer cell adaptation to stress. Since several NMD inhibitors are already available in the clinic to treat genetic diseases, these compounds could be redirected to treat cancer patients, pending the comprehension of these variegated NMD regulation mechanisms. Ideally, an effective strategy should exploit the anti-tumor advantages of NMD inhibition and simultaneously preserve its intrinsic tumor suppressor functions. The targeting of NMD could provide a new therapeutic opportunity, increasing the immunogenicity of tumors and potentially boosting the efficacy of the immunotherapy agents now available for cancer treatment.

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Section: Nmd As a Tumor Suppressor Interconnected With The Tumor Microenvironment (Tme)mentioning

confidence: 99%

Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy

Bongiorno

Colombo

Lecis

2021

J Exp Clin Cancer Res

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“…SMG7 is a nonsense-mediated decay complex protein, and is responsible for the surveillance and degradation of abnormal RNAs [ 28 ]. SMG7 may directly interact with p53, regulate p53 stability, and lead to p53-mediated DNA damage response [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiles and bioinformatics analysis in lung samples from ovalbumin-induced asthmatic mice

Song

Jiang²,

Bai³

et al. 2023

BMC Pulm Med

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Background Asthma is characterized by chronic inflammation and airway remodeling. However, limited study is conducted on the gene expression profiles of ovalbumin (OVA) induced asthma in mice. Here, we explored the gene expression profiles in lung tissues from mice with OVA-induced asthma using microarray and bioinformatics analysis. Methods For establishment of OVA-induced asthma model, mice first received intraperitoneal sensitization with OVA on day 0, 7 and 14, followed by atomizing inhalation of OVA 3 times a week for 8 weeks. The lung tissues were collected and subjected to microarray analysis, bioinformatics analysis and expression validation. Results Microarray data of lung tissues suggested that 3754 lncRNAs and 2976 mRNAs were differentially expressed in lung tissues between control and asthmatic mice, including 1647 up-regulated and 2106 down-regulated lncRNAs, and 1201 up-regulated and 1766 down-regulated mRNAs. GO analysis displayed that the up-regulated genes were enriched in inflammatory response, leukocyte migration involved in inflammatory response, and Notch signaling pathway. KEGG pathway analysis indicated that the enriched pathway terms of the up-regulated gene included Toll-like receptor signaling pathway and Th17 cell differentiation signaling pathway. Additionally, based on the previously published literatures on asthma and inflammation, we screened out down-regulated genes, such as Smg7, Sumo2, and Stat5a, and up-regulated genes, such as Myl9, Fos and Tlr4. According to the mRNA-lncRNA co-expression network, we selected lncRNAs associated with above genes, including the down-regulated lncRNAs of NONMMUT032848, NONMMUT008873, NONMMUT009478, and NONMMUT006807, and the up-regulated lncRNAs of NONMMUT052633, NONMMUT05340 and NONMMUT042325. The expression changes of the above genes were validated in lung tissues by real-time quantitaive PCR and Western blot. Conclusions Overall, we performed gene microarray on lung samples from OVA-induced asthmatic mice and summarized core mRNAs and their related lncRNAs. This study may provide evidence for further research on the therapeutic targets of asthma.

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“…Emerging evidence has demonstrated that lncRNAs are involved in tumor development. [57][58][59][60][61][62] Nevertheless, the biological role and mechanism of lncRNAs in PCa BM remain largely undiscovered. As far as we know, PCAT6 was first systematically assessed in PCa BM.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, revealing the precise mechanisms underlying BM and developing novel potential therapeutic targets are urgently needed for the prevention and treatment of BM. Emerging evidence has demonstrated that lncRNAs are involved in tumor development 57–62 . Nevertheless, the biological role and mechanism of lncRNAs in PCa BM remain largely undiscovered.…”

Section: Discussionmentioning

confidence: 99%

m⁶A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2‐mediated IGF1R mRNA stabilization

Lang

Yin

Lin

et al. 2021

Clinical & Translational Med

102

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Background Bone metastasis is the leading cause of tumor‐related death in prostate cancer (PCa) patients. Long noncoding RNAs (lncRNAs) have been well documented to be involved in the progression of multiple cancers. Nevertheless, the role of lncRNAs in PCa bone metastasis remains largely unclear. Methods The expression of prostate cancer‐associated transcripts was analyzed in published datasets and further verified in clinical samples and cell lines by RT‐qPCR and in situ hybridization assays. Colony formation assay, MTT assay, cell cycle analysis, EdU assay, Transwell migration and invasion assays, wound healing assay, and in vivo experiments were carried out to investigate the function of prostate cancer‐associated transcript 6 ( PCAT6 ) in bone metastasis and tumor growth of PCa. Bioinformatic analysis, RNA pull‐down, and RIP assays were conducted to identify the proteins binding to PCAT6 and the potential targets of PCAT6 . The therapeutic potential of targeting PCAT6 by antisense oligonucleotides (ASO) was further explored in vivo . Results PCAT6 was upregulated in PCa tissues with bone metastasis and increased PCAT6 expression predicted poor prognosis in PCa patients. Functional experiments found that PCAT6 knockdown significantly inhibited PCa cell invasion, migration, and proliferation in vitro , as well as bone metastasis and tumor growth in vivo . Mechanistically, METTL3 ‐mediated m 6 A modification contributed to PCAT6 upregulation in an IGF2BP2 ‐dependent manner. Furthermore, PCAT6 upregulated IGF1R expression by enhancing IGF1R mRNA stability through the PCAT6 / IGF2BP2 / IGF1R RNA‐protein three‐dimensional complex. Importantly, PCAT6 inhibition by ASO in vivo showed therapeutic potential against bone metastasis in PCa. Finally, the clinical correlation of METTL3 , IGF2BP2 , IGF1R , and PCAT6 was further demonstrated in PCa tissues and cells. Conclusions Our study uncovers a novel molecular mechanism by which the m 6 A‐induced PCAT6 / IGF2BP2 / IGF1R axis promotes PCa bone metastasis and tumor growth, suggesting th...

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Nonsense‐mediated decay factor SMG7 sensitizes cells to TNFα‐induced apoptosis via CYLD tumor suppressor and the noncoding oncogene Pvt1

Cited by 8 publications

References 59 publications

Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy

Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy

Gene expression profiles and bioinformatics analysis in lung samples from ovalbumin-induced asthmatic mice

m⁶A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2‐mediated IGF1R mRNA stabilization

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Nonsense‐mediated decay factor SMG7 sensitizes cells to TNFα‐induced apoptosis via CYLD tumor suppressor and the noncoding oncogene Pvt1

Cited by 8 publications

References 59 publications

Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy

Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy

Gene expression profiles and bioinformatics analysis in lung samples from ovalbumin-induced asthmatic mice

m6A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2‐mediated IGF1R mRNA stabilization

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m⁶A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2‐mediated IGF1R mRNA stabilization