RP11‐81H3.2 promotes gastric cancer progression through miR‐339‐HNRNPA1 interaction network

Chen, Fenrong; Sha, Su‐Mei; Wang, Shen‐Hao; Shi, Haitao; Liu, Dong; Liu, Dong; Cheng, Yan; An, Malaviya; Wang, Yan; Zhang, Jun

doi:10.1002/cam4.2867

Cited by 13 publications

(4 citation statements)

References 32 publications

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“…Dysregulation of hnRNPA1 has been associated with various diseases, including cancer [ 38 ]. For example, hnRNPA1 was overexpressed in lung carcinoma, GC, and colorectal cancer [ 39 ] and has been correlated with poor prognosis in hepatocellular carcinoma and breast cancer [ 40 , 41 ]. In this study, GC patients with high levels of hnRNPA1 had unfavorable overall survival in TCGA database, and upregulation of hnRNPA1 protein expression was observed in OIP5-AS1-overexpressing GC cells.…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine modification of OIP5-AS1 promotes glycolysis, tumorigenesis, and metastasis of gastric cancer by inhibiting Trim21-mediated hnRNPA1 ubiquitination and degradation

Xie,

Liu,

et al. 2023

Gastric Cancer

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Background Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been demonstrated to play vital roles in development and progression of tumors such as gastric cancer (GC). However, the detailed molecular mechanism of OIP5-AS1 has not been completely elucidated. Our study aimed to investigate the role and the epigenetic regulation mechanism of OIP5-AS1 in GC. Methods OIP5-AS1 expression in GC tissues was detected by RT-qPCR. Loss- and gain-of-function experiments were conducted to assess the biological function of OIP5-AS1 in vitro and in vivo. The interaction of OIP5-AS1 with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) or heterogeneous nuclear nucleoprotein A1 (hnRNPA1) was verified by bioinformatics analysis, RNA pull-down assays, and RNA immunoprecipitation assays. Results In this study, we identified that OIP5-AS1 is specifically overexpressed in GC tumor tissues and cell lines and correlated with a poor prognosis. The loss of OIP5-AS1 suppressed the proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and glycolysis of GC cells, but the ectopic expression of OIP5-AS1 had the opposite impact. Meanwhile, knockdown of OIP5-AS1 inhibited tumor growth in patient-derived xenograft models, as well as repressed tumor metastasis. Mechanistically, IGF2BP3 could bind to OIP5-AS1 by N6-methyladenosine (m6A) modification sites on OIP5-AS1, thereby stabilizing OIP5-AS1. Moreover, OIP5-AS1 prevented Trim21-mediated ubiquitination and degradation of hnRNPA1, stabilizing hnRNPA1 protein and promoting the malignant progression of GC by regulating PKM2 signaling pathway. Conclusions In conclusion, this study highlighted that OIP5-AS1 is an oncogenic m6A-modified long non-coding RNA (lncRNA) in GC and that IGF2BP3/OIP5-AS1/hnRNPA1 axis may provide a potential diagnostic or prognostic target for GC.

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Section: Discussionmentioning

confidence: 99%

N6-methyladenosine modification of OIP5-AS1 promotes glycolysis, tumorigenesis, and metastasis of gastric cancer by inhibiting Trim21-mediated hnRNPA1 ubiquitination and degradation

Xie,

Liu,

et al. 2023

Gastric Cancer

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“…The RP-11 lnRNAs we found in our study have not yet been described to be associated with any specific diseases. However, several other RP-11 lncRNAs have previously been shown to play a role in the progression of different types of cancer, including colorectal cancer ( 52 ), HCC ( 53 ), ovarian cancer ( 54 ) and gastric cancer ( 55 ). Given cancer was the top disease linked to the NET-associated genes in our pathway analysis, future studies may investigate the potential link between these lncRNAs, NETs and cancer.…”

Section: Discussionmentioning

confidence: 99%

Common and Rare Variants Genetic Association Analysis of Circulating Neutrophil Extracellular Traps

et al. 2021

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IntroductionNeutrophils contribute to host defense through different mechanisms, including the formation of neutrophil extracellular traps (NETs). The genetic background and underlying mechanisms contributing to NET formation remain unclear.Materials and MethodsWe performed a genome-wide association study (GWAS) and exome-sequencing analysis to identify common and rare genetic variants associated with plasma myeloperoxidase (MPO)-DNA complex levels, a biomarker for NETs, in the population-based Rotterdam Study cohort. GWAS was performed using haplotype reference consortium(HRC)-imputed genotypes of common variants in 3,514 individuals from the first and 2,076 individuals from the second cohort of the Rotterdam Study. We additionally performed exome-sequencing analysis in 960 individuals to investigate rare variants in candidate genes.ResultsThe GWAS yielded suggestive associations (p-value < 5.0 × 10−6) of SNPs annotated to four genes. In the exome-sequencing analysis, a variant in TMPRSS13 gene was significantly associated with MPO-DNA complex levels (p-value < 3.06×10−8). Moreover, gene-based analysis showed ten genes (OR10H1, RP11-461L13.5, RP11-24B19.4, RP11-461L13.3, KHDRBS1, ZNF200, RP11-395I6.1, RP11-696P8.2, RGPD1, AC007036.5) to be associated with MPO-DNA complex levels (p-value between 4.48 × 10−9 and 1.05 × 10−6). Pathway analysis of the identified genes showed their involvement in cellular development, molecular transport, RNA trafficking, cell-to-cell signaling and interaction, cellular growth and proliferation. Cancer was the top disease linked to the NET-associated genes.ConclusionIn this first GWAS and exome-sequencing analysis of NETs levels, we found several genes that were associated with NETs. The precise mechanism of how these genes may contribute to neutrophil function or the formation of NETs remains unclear and should be further investigated in experimental studies.

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“…The general function of RP11-81H3.2 remains largely unknown. Recently, a number of studies have investigated the role of RP11-81H3.2 in cancer progression and reported that RP11-81H3.2 promotes the progression of gastric cancer via the miR-339/HNRNPA1 axis and that of hepatocellular carcinoma via the miR-490-3p/consequential tankyrase 2 axis ( 31 , 32 ). Other roles of RP11-81H3.2 have not been documented.…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA RP11‑81H3.2 suppresses apoptosis by targeting microRNA‑1539/COL2A1 in human nucleus pulposus cells

Lin¹,

Peng²,

Zhou³

et al. 2021

Exp Ther Med

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Intervertebral disk degeneration (IDD) is a severe health problem that results in lower back pain and disability. Previous evidence has indicated that excessive apoptosis of nucleus pulposus (NP) cell is involved in the occurrence and development of IDD. However, the underlying mechanisms regulating NP cell apoptosis are unclear. The present study aimed to investigate the function of a novel long non-coding RNA RP11-81H3.2 in modulating NP cell apoptosis and the potential underlying mechanisms. The results demonstrated that the RP11-81H3.2 expression levels were significantly decreased in NP tissues from patients with IDD compared with those from healthy controls, and that lower expression levels were associated with higher-grade disk degeneration. Functionally, RP11-81H3.2 silencing promoted apoptosis and decreased the viability of NP cells derived from tissue samples of patients with IDD, whereas RP11-81H3.2 overexpression induced opposite effects. Bioinformatics analysis, luciferase assays and reverse transcription-quantitative PCR revealed that microRNA (miR)-1539 was a direct target of RP11-81H3.2. A mechanistic analysis demonstrated that RP11-81H3.2 functioned as an RNA sink to downregulate miR-1539, which led to the upregulation of collagen type 2 α 1 chain (COL2A1), a target of miR-1539. Collectively, the present results suggested that lower RP11-81H3.2 expression levels were associated with higher-grade IDD, and that RP11-81H3.2 inhibited NP cell apoptosis by decreasing the levels of miR-1539 to increase COL2A1 expression levels. The present study identified a beneficial role of RP11-81H3.2 against NP cell apoptosis.

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RP11‐81H3.2 promotes gastric cancer progression through miR‐339‐HNRNPA1 interaction network

Cited by 13 publications

References 32 publications

N6-methyladenosine modification of OIP5-AS1 promotes glycolysis, tumorigenesis, and metastasis of gastric cancer by inhibiting Trim21-mediated hnRNPA1 ubiquitination and degradation

N6-methyladenosine modification of OIP5-AS1 promotes glycolysis, tumorigenesis, and metastasis of gastric cancer by inhibiting Trim21-mediated hnRNPA1 ubiquitination and degradation

Common and Rare Variants Genetic Association Analysis of Circulating Neutrophil Extracellular Traps

Long non‑coding RNA RP11‑81H3.2 suppresses apoptosis by targeting microRNA‑1539/COL2A1 in human nucleus pulposus cells

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