Dataset Information

Long noncoding RNA ZFAS1 promotes tumorigenesis and metastasis in nasopharyngeal carcinoma by sponging miR-892b to up-regulate LPAR1 expression.

ABSTRACT:

Objective

In this study, we explored the NPC-specific expression of ZFAS1 and the mechanism of ZFAS1-mediated growth, aggressiveness and tumorigenesis in NPC.

Methods

The expression profile of lncRNAs was detected in NPC tissues and matching para-carcinoma tissues using microarray analysis. LncRNA-miRNA and miRNA-mRNA interaction networks were constructed using the miRcode v11 and TargetScanHuman v7.2 web server and then validated using dual-luciferase assay. Western blot and RT-qPCR were performed to detect protein and RNA expression. The effects of ZFAS1, miR-892b and LPAR1 dysregulation on the proliferative, migratory and invasive abilities of NPC cells were observed using colony formation, cell counting kit-8 (CCK-8) and transwell assays in vitro. In vivo, a xenograft nude mouse model was established to detect the impact of ZFAS1 dysregulation on the tumorigenicity of NPC cells.

Results

The expression of multiple lncRNAs, of which ZFAS1 was up-regulated, was dysregulated in NPC tissues. ZFAS1 directly targeted miR-892b, and miR-892b negatively regulated the expression of downstream LPAR1. The proliferation, migration and invasion of NPC cells could be largely enhanced by the downregulation of miR-892b as well as the up-regulation of ZFAS1 and LPAR1, while the overexpression of miR-892b and the downregulation of ZFAS1 and LPAR1 decreased these abilities. In nude mice, the growth of tumour xenografts formed by HONE1 cells was significantly suppressed when ZFAS1 was silenced.

Conclusion

The study demonstrated that lncRNA ZFAS1 may act as a promoter of tumorigenesis and metastasis in nasopharyngeal carcinoma, by up-regulating the expression of LPAR1 in a miR-892b-dependent manner.

SUBMITTER: Peng J

PROVIDER: S-EPMC6991699 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long noncoding RNA ZFAS1 promotes tumorigenesis and metastasis in nasopharyngeal carcinoma by sponging miR-892b to up-regulate LPAR1 expression.

Peng Jiaojiao J Liu Feng F Zheng Hong H Wu Qi Q Liu Shixi S

Journal of cellular and molecular medicine 20191218 2

<h4>Objective</h4>In this study, we explored the NPC-specific expression of ZFAS1 and the mechanism of ZFAS1-mediated growth, aggressiveness and tumorigenesis in NPC.<h4>Methods</h4>The expression profile of lncRNAs was detected in NPC tissues and matching para-carcinoma tissues using microarray analysis. LncRNA-miRNA and miRNA-mRNA interaction networks were constructed using the miRcode v11 and TargetScanHuman v7.2 web server and then validated using dual-luciferase assay. Western blot and RT-q ...[more]

PMID: 31851778

Similar Datasets

Project description:RationaleCircular RNAs (circRNAs) have been demonstrated to contribute to esophageal cancer progression. CircBCAR3 (hsa_circ_0007624) is predicted to be differentially expressed in esophageal cancer by bioinformatics analysis. We investigated the oncogenic roles and biogenesis of circBCAR3 in esophageal carcinogenesis.MethodsFunctions of circBCAR3 on cancer cell proliferation, migration, invasion, and ferroptosis were explored using the loss-of-function assays. A xenograft mouse model was used to reveal effects of circBCAR3 on xenograft growth and lung metastasis. The upstream and downstream mechanisms of circBCAR3 were investigated by bioinformatics analysis and confirmed by RNA immunoprecipitation and luciferase reporter assays. The dysregulated genes in hypoxia-induced esophageal cancer cells were identified using RNA-seq.ResultsCircBCAR3 was highly expressed in esophageal cancer tissues and cells and its expression was increased by hypoxia in vitro. Silencing of circBCAR3 repressed the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells in vitro, as well as inhibited the growth and metastasis of esophageal xenograft in mice in vivo. The hypoxia-induced promotive effects on esophageal cancer cell migration and ferroptosis were rescued by circBCAR3 knockdown. Mechanistically, circBCAR3 can interact with miR-27a-3p by the competitive endogenous RNA mechanism to upregulate transportin-1 (TNPO1). Furthermore, our investigation indicated that splicing factor quaking (QKI) is a positive regulator of circBCAR3 via targeting the introns flanking the hsa_circ_0007624-formed exons in BCAR3 pre-mRNA. Hypoxia upregulates E2F7 to transcriptionally activate QKI.ConclusionOur research demonstrated that splicing factor QKI promotes circBCAR3 biogenesis, which accelerates esophageal cancer tumorigenesis via binding with miR-27a-3p to upregulate TNPO1. These data suggested circBCAR3 as a potential target in the treatment of esophageal cancer. Hypoxia induces the upregulation of E2F7, which transcriptionally activates QKI in esophageal cancer cells. QKI increases the formation of circBCAR3 by juxtaposing the circularized exons. CircBCAR3 binds with miR-27a-3p to promote TNPO1 expression. CircBCAR3 promoted the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells by miR-27a-3p.

Dataset Information

Long noncoding RNA ZFAS1 promotes tumorigenesis and metastasis in nasopharyngeal carcinoma by sponging miR-892b to up-regulate LPAR1 expression.

Objective

Methods

Results

Conclusion

Publications

Long noncoding RNA ZFAS1 promotes tumorigenesis and metastasis in nasopharyngeal carcinoma by sponging miR-892b to up-regulate LPAR1 expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets