Dataset Information

Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression.

ABSTRACT: Long intergenic non-protein-coding RNA 324 (LINC00324) is abnormally expressed in multiple human cancer types and plays an important role in cancer initiation and progression. This study showed that LINC00324 was expressed at higher levels in retinoblastoma (RB) tumors and cell lines than in control samples. Increased LINC00324 expression closely correlated with the TNM stage, optic nerve invasion, and shorter overall survival among patients with RB. The knockdown of LINC00324 decreased RB cell proliferation, colony formation, migration, and invasion, and promoted apoptosis and cell cycle arrest in vitro as well as hindered tumor growth in vivo. With respect to the mechanism, LINC00324 acted as a competing endogenous RNA for microRNA-769-5p (miR-769-5p) in RB cells. The mRNA of signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR-769-5p in RB cells. Rescue experiments indicated that restoration of STAT3 expression attenuated the tumor-suppressive actions of miR-769-5p in RB cells. Downregulation of miR-769-5p or restoration of STAT3 almost completely reversed the effects of LINC00324 knockdown on RB cells. Our findings describe a novel RB-related LINC00324-miR-769-5p-STAT3 axis that is implicated in the malignancy of RB in vitro and in vivo. This study may point to innovative therapeutic targets in RB.

SUBMITTER: Dong Y

PROVIDER: S-EPMC7244063 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression.

Dong Yi Y Wan Guangming G Yan Panshi P Qian Cheng C Li Fuzhen F Peng Guanghua G

Aging 20200505 9

Long intergenic non-protein-coding RNA 324 (LINC00324) is abnormally expressed in multiple human cancer types and plays an important role in cancer initiation and progression. This study showed that LINC00324 was expressed at higher levels in retinoblastoma (RB) tumors and cell lines than in control samples. Increased LINC00324 expression closely correlated with the TNM stage, optic nerve invasion, and shorter overall survival among patients with RB. The knockdown of LINC ...[more]

PMID: 32369777

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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 noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression.

Publications

Long noncoding RNA <i>LINC00324</i> promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression.

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