Dataset Information

LncRNA-PLACT1 sustains activation of NF-?B pathway through a positive feedback loop with I?B?/E2F1 axis in pancreatic cancer.

ABSTRACT: BACKGROUND:The activation of NF-?B signaling pathway is regarded as the dominant process that correlates with tumorigenesis. Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play crucial roles in sustaining the NF-?B signaling pathway. However, the underlying mechanisms have not yet been elucidated. METHODS:The expression and clinical features of PLACT1 were analyzed in a 166-case cohort of PDAC by qRT-PCR and in situ hybridization. The functional role of PLACT1 was evaluated by both in vitro and in vivo experiments. Chromatin isolation by RNA purification assays were utilized to examine the interaction of PLACT1 with I?B? promoter. RESULTS:We identified a novel lncRNA-PLACT1, which was significantly upregulated in tumor tissues and correlated with progression and poor survival in PDAC patients. Moreover, PLACT1 promoted the proliferation and invasion of PDAC cells in vitro. Consistently, PLACT1 overexpression fostered the progression of PDAC both in orthotopic and lung metastasis mice models. Mechanistically, PLACT1 suppressed I?B? expression by recruiting hnRNPA1 to I?B? promoter, which led to increased H3K27me3 that decreased the transcriptional level of I?B?. Furthermore, E2F1-mediated overexpression of PLACT1 modulated the progression of PDAC by sustained activation of NF-?B signaling pathway through forming a positive feedback loop with I?B?. Importantly, administration of the NF-?B signaling pathway inhibitor significantly suppressed PLACT1-induced sustained activation of NF-?B signaling pathway, leading to reduced tumorigenesis in vivo. CONCLUSIONS:Our findings suggest that PLACT1 provides a novel epigenetic mechanism involved in constitutive activation of NF-?B signaling pathway and may represent a new therapeutic target of PDAC.

SUBMITTER: Ren X

PROVIDER: S-EPMC7033942 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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lncRNA-PLACT1 sustains activation of NF-κB pathway through a positive feedback loop with IκBα/E2F1 axis in pancreatic cancer.

Ren Xiaofan X Chen Changhao C Luo Yuming Y Liu Mingyang M Li Yuting Y Zheng Shangyou S Ye Huilin H Fu Zhiqiang Z Li Min M Li Zhihua Z Chen Rufu R

Molecular cancer 20200221 1

<h4>Background</h4>The activation of NF-κB signaling pathway is regarded as the dominant process that correlates with tumorigenesis. Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play crucial roles in sustaining the NF-κB signaling pathway. However, the underlying mechanisms have not yet been elucidated.<h4>Methods</h4>The expression and clinical features of PLACT1 were analyzed in a 166-case cohort of PDAC by qRT-PCR and in situ hybridization. The functional role of PLA ...[more]

PMID: 32085715

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Dataset Information

LncRNA-PLACT1 sustains activation of NF-?B pathway through a positive feedback loop with I?B?/E2F1 axis in pancreatic cancer.

Publications

lncRNA-PLACT1 sustains activation of NF-κB pathway through a positive feedback loop with IκBα/E2F1 axis in pancreatic cancer.

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