The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma

Liu, Chen; Karam, Rachid; Zhou, Yingqi; Su, Fang; Ji, Yuan; Li, Gang; Xu, Guo‐Tong; Lü, Lixia; Wang, Chongren; Song, Meiyi; Zhu, Jianxun; Wang, Yiran; Zhao, Yifan; Foo, Wai Chin; Zuo, Mingxin; Valasek, Mark A.; Javle, Milind; Wilkinson, Miles; Lu, Yi

doi:10.1038/nm.3548

Cited by 117 publications

(114 citation statements)

References 21 publications

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“…We speculate that the aberrations in NMD caused by genetic alterations in the UPF1 gene lead to different disease outcomes, depending on the cell type. In premalignant glandular pancreatic cells, this may lead to reprogramming towards a squamous, more malignant state (5). In lung epithelial cells, NMD perturbation may drive a proinflammatory response, as suggested by our results herein.…”

Section: Author Contributionssupporting

confidence: 55%

The nonsense-mediated RNA decay pathway is disrupted in inflammatory myofibroblastic tumors

Lü¹,

Plank²,

Su³

et al. 2016

Journal of Clinical Investigation

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Section: Author Contributionssupporting

confidence: 55%

The nonsense-mediated RNA decay pathway is disrupted in inflammatory myofibroblastic tumors

Lü¹,

Plank²,

Su³

et al. 2016

Journal of Clinical Investigation

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“…The patient was then enrolled on a phase I trial involving a combination PI3K and MEK inhibitor, and experienced a clinical benefit in the form of a dramatic decrease in his pain, along with tumor response [36] . Another genetic analysis done recently looked at 23 patients with ASCP through genomic sequencing and showed a mutation of the UPF1 gene, which encodes a RNA helicase essential for the highly conserved RNA degradation pathway, nonsense-mediated RNA decay [37] . This mutation was not seen in the adjacent normal tissue of these patient samples.…”

mentioning

confidence: 99%

“…This mutation was not seen in the adjacent normal tissue of these patient samples. The pathways that UPF1 is implicated in are not all known but appear to be involved in the normal splicing of RNA, affecting such genes as p53 [37] .…”

mentioning

confidence: 99%

Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review

Borazanci

Millis

Korn

et al. 2015

WJGO

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Adenosquamous carcinoma of the pancreas (ASCP) is a rare entity. Like adenocarcinoma of the pancreas, overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP. Molecular characterization revealed overexpression in MRP1 (80%), MGMT (79%), TOP2A (75), RRM1 (42%), TOPO1 (42%), PTEN (45%), CMET (40%), and C-KIT (10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered

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“…Also, UPF1 is also involved in cell proliferation and differentiation by promoting the proliferative, undifferentiation state or the decay of mRNAs encoding many other proteins that oppose the proliferative, undifferentiated cell state [15]. Another study has shown that UPF1 is down-regulated and commonly mutated in pancreatic adenosquamous carcinoma [16]. However, no studies have investigated the exact activities of UPF1 in human gastric cancer, which promotes us to explore its roles in gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1

Li¹,

Geng²,

Ren³

et al. 2017

Cell Physiol Biochem

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Background/Aims: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in numerous cancers. However, whether MALAT1 is regulated and the related mechanisms in gastric cancer remain unclear. Methods: Immunohistochemistry and qRT-PCR analyses were used to detect the expression levels of UPF1 and MALAT1 in gastric cancer and adjacent normal tissues. MTT, cell cycle, apoptosis and transwell assays were performed to examine the effects of UPF1 on cell cycle progression, cell proliferation, apoptosis, migration and invasion. Additionally, sodium bisulfate sequencing was used to test the promoter hypermethylation on UPF1 in gastric tumor tissues. Finally, RNA immunoprecipitation and luciferase reporter analyses demonstrated that UPF1 directly bound with MALAT1. Results: The expression of UPF1 was significantly downregulated in gastric cancer and negatively correlated with MALAT1 expression. Patients with lower expression of UPF1 had poorer prognosis than those with higher expression. Overexpression of UPF1 inhibited cell proliferation, cell cycle progression, cell migration and invasion, and promoted cell apoptosis in gastric cancer cells. Moreover, the UPF1-mediated inhibition of gastric cancer progression was reversed by overexpression of MALAT1. A profound downregulation of UPF1 in gastric tumor tissues was due to promoter hypermethylation. Overexpression of UPF1 increased nonsense-mediated mRNA decay (NMD) efficiency and thus led to downregulation of MALAT1. Conclusion: Our results demonstrate that UPF1 is a potential modulator of MALAT1 and that UPF1/MALAT1 pathway could be a therapeutic target for gastric cancer.

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The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma

Cited by 117 publications

References 21 publications

The nonsense-mediated RNA decay pathway is disrupted in inflammatory myofibroblastic tumors

The nonsense-mediated RNA decay pathway is disrupted in inflammatory myofibroblastic tumors

Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1

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