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

Abstract

Background: 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. 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 IκBα 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 IκBα expression by recruiting hnRNPA1 to IκBα promoter, which led to increased H3K27me3 that decreased the transcriptional level of IκBα. Furthermore, E2F1mediated overexpression of PLACT1 modulated the progression of PDAC by sustained activation of NF-κB signaling pathway through forming a positive feedback loop with IκBα. Importantly, administration of the NF-κB signaling pathway inhibitor significantly suppressed PLACT1-induced sustained activation of NF-κB signaling pathway, leading to reduced tumorigenesis in vivo.

PGM5-AS1 Inhibits the Malignant Phenotype of Colon Cancer Cells by Regulating PAEP and NME1

“…According to previous studies, abnormally high expression of lncRNA may be induced by transcription activators, stress, DNA methylation, and exosomes [47][48][49][50][51]. For example, the tumor suppressor gene p53 can transcriptionally activate lncRNA Pvt1b [47].…”

“…continuously activates the NF-kappaB signaling pathway through a positive feedback loop to regulate the process of pancreatic ductal adenocarcinoma (PDAC) [48]. Stress-induced lncRNA LASTR is up-regulated in hypoxic breast cancer [49].…”

<p>LncRNA GAS8-AS1 Inhibits Ovarian Cancer Progression Through Activating Beclin1-Mediated Autophagy</p>

“…Xenograft model is common used in exploring tumor occurrence and growth. 38 Our tumorigenesis assay showed GAS8-AS1 suppressed OC progression and activated Beclin1 mediated autophagy.…”

Knockdown long noncoding RNA SLC8A1-AS1 attenuate cell invasion and migration in glioma via suppression of Wnt-β catenin signaling pathways

“…To elucidate the possible mechanism by which lncRNA SLC8A1-AS1 regulates the proliferation, clone formation, migration and invasion of glioma cell, Western-blot analysis of the key molecular factors of cancer-related pathways, such as Hippo pathway, Wnt/β-catenin pathway was performed. The Wnt/βcatenin pathway plays a key role in tumor EMT [17][18][19]. GSK-3β is one of the components of the destruction complex in the Wnt/β-catenin signaling [20].…”