Dataset Information

Long non-coding RNA PXN-AS1 suppresses pancreatic cancer progression by acting as a competing endogenous RNA of miR-3064 to upregulate PIP4K2B expression.

ABSTRACT:

Background

Dysregulation of microRNAs (miRNAs) play critical roles in cancerous processes. Although miR-3064 was reported to be an important tumor suppressor in ovarian cancer, the cellular impact of miR-3064 on pancreatic cancer (PC) progression, its downstream target genes and upstream mechanisms that control the expression of miR-3064 remain to be fully clarified.

Methods

We compared miRNA expression profiles between PC tissues compared with normal tissues using a miRNA microarray analysis of clinical samples, and screened the identified miRNAs for their influence on cell proliferation. We measured the expression of miR-3064 in PC tissues and PC cell lines using quantitative real-time PCR assays. Gain- and loss-of-function experiments were conducted to explore the biologic significance of miR-3064 in PC progression both in vitro and in vivo. The interactions between miR-3064 and long noncoding RNA (lncRNA) PXN-AS1 was verified using the luciferase reporter assay and RNA immunoprecipitation assay.

Results

We showed that miR-3064 was significantly overexpressed in PC tissues compared to normal tissues. High miR-3064 was associated with worse prognosis in patients with PC. Functionally, ectopic expression of miR-3064 promoted the proliferation, invasion, clone formation and sphere formation of PC cells in vitro and stimulated PC growth in vivo, while specific knockdown of miR-3064 or CRISPR/Cas9-mediated knockout of miR-3064 resulted in opposite phenotypes. Further investigation revealed that miR-3064 directly targeted PIP4K2B, which was reduced in PC tissues and attenuated PC cell proliferation, invasion and sphere formation induced by miR-3064. Importantly, lncRNA PXN-AS1 expression was downregulated in PC samples, and it directly interacted with miR-3064 and suppressed its levels in PC cells. Enforced expression of PXN-AS1 remarkably decreased cell proliferation, invasion and sphere formation, while re-expression of miR-3064 abrogated these effects of PXN-AS1.

Conclusions

MiR-3064, a key oncogenic miRNA, could promote PC cell growth, invasion and sphere formation via downregulating the levels of tumor suppressor PIP4K2B. PXN-AS1 functioned as a sponge to suppress the expression of miR-3064. These observations offer fresh insight into the mechanisms through which miR-3064 modulates the development of PC.

SUBMITTER: Yan J

PROVIDER: S-EPMC6727519 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Long non-coding RNA PXN-AS1 suppresses pancreatic cancer progression by acting as a competing endogenous RNA of miR-3064 to upregulate PIP4K2B expression.

Yan Jiayan J Jia Yunxi Y Chen Han H Chen Wei W Zhou Xiaoying X

Journal of experimental & clinical cancer research : CR 20190905 1

<h4>Background</h4>Dysregulation of microRNAs (miRNAs) play critical roles in cancerous processes. Although miR-3064 was reported to be an important tumor suppressor in ovarian cancer, the cellular impact of miR-3064 on pancreatic cancer (PC) progression, its downstream target genes and upstream mechanisms that control the expression of miR-3064 remain to be fully clarified.<h4>Methods</h4>We compared miRNA expression profiles between PC tissues compared with normal tissues using a miRNA microar ...[more]

PMID: 31488171

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Project description:Long noncoding RNAs (lncRNAs) are involved in numerous cellular processes. Increasing evidence suggests that some lncRNAs function in immunity through various complex mechanisms. However, implication of a large fraction of lncRNAs in antiviral innate immunity remains uncharacterized. Here, we identified an lncRNA called lncRNA IFITM4P that was transcribed from interferon-induced transmembrane protein 4 pseudogene (IFITM4P), a pseudogene belonging to the interferon-induced transmembrane protein (IFITM) family. We found that expression of lncRNA IFITM4P was significantly induced by infection with several viruses, including influenza A virus (IAV). Importantly, lncRNA IFITM4P acted as a positive regulator of innate antiviral immunity. Ectopic expression of lncRNA IFITM4P significantly suppressed IAV replication in vitro, whereas IFITM4P deficiency promoted viral production. We further observed that expression of lncRNA IFITM4P was upregulated by interferon (IFN) signaling during viral infection, and altering the expression of this lncRNA had significant effects on the mRNA levels of several IFITM family members, including IFITM1, IFITM2, and IFITM3. Moreover, lncRNA IFITM4P was identified as a target of the microRNA miR-24-3p, which represses mRNA of IFITM1, IFITM2, and IFITM3. The experiments demonstrated that lncRNA IFITM4P was able to cross-regulate the expression of IFITM family members as a competing endogenous RNA (ceRNA), leading to increased stability of these IFITM mRNAs. Together, our results reveal that lncRNA IFITM4P, as a ceRNA, is involved in innate immunity against viral infection through the lncRNA IFITM4P-miR-24-3p-IFITM1/2/3 regulatory network. IMPORTANCE lncRNAs play important roles in various biological processes, but their involvement in host antiviral responses remains largely unknown. In this study, we revealed that the pseudogene IFITM4P belonging to the IFITM family can transcribe a functional long noncoding RNA termed lncRNA IFITM4P. Importantly, results showed that lncRNA IFITM4P was involved in innate antiviral immunity, which resembles some interferon-stimulated genes (ISGs). Furthermore, lncRNA IFITM4P was identified as a target of miR-24-3p and acts as a ceRNA to inhibit the replication of IAV through regulating the mRNA levels of IFITM1, IFITM2, and IFITM3. These data provide new insight into the role of a previously uncharacterized lncRNA encoded by a pseudogene in the host antiviral response and a better understanding of the IFITM antiviral network.

Dataset Information

Long non-coding RNA PXN-AS1 suppresses pancreatic cancer progression by acting as a competing endogenous RNA of miR-3064 to upregulate PIP4K2B expression.

Background

Methods

Results

Conclusions

Publications

Long non-coding RNA PXN-AS1 suppresses pancreatic cancer progression by acting as a competing endogenous RNA of miR-3064 to upregulate PIP4K2B expression.

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