Integrative Analysis of NSCLC Identifies LINC01234 as an Oncogenic lncRNA that Interacts with HNRNPA2B1 and Regulates miR-106b Biogenesis

Chen, Zhenyao; Chen, Xin; Lei, Tianyao; Gu, Yu; Gu, Jianqin; Huang, Jiana; Lu, Binfeng; Li, Yuan; Sun, Ming; Wang, Zhaoxia

doi:10.1016/j.ymthe.2020.03.010

Cited by 76 publications

(62 citation statements)

References 43 publications

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“…It is reported that HNRNPA2B1 could selectively bind to m 6 A-containing transcripts via the “m 6 A-switch,” a mechanism in which m 6 A weakens Watson–Crick base pairing to destabilize the RNA hairpin structure and thereby exposes the single stranded hnRNP binding motif ( 37 ). HNRNPA2B1 has been reported to be a RNA-binding protein involved in different cancer progression ( 38 – 40 ). HNRNPA2B1 could interact with LINC01234 to promote lung cancer progression ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…HNRNPA2B1 has been reported to be a RNA-binding protein involved in different cancer progression ( 38 – 40 ). HNRNPA2B1 could interact with LINC01234 to promote lung cancer progression ( 38 ). It also reported that HNRNPA2B1 promoted malignant capability and inhibited apoptosis via down-regulation of Lin28B expression in ovarian cancer ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

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m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Guo

Wang

et al. 2020

Front. Oncol.

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N6-methyladenosine (m 6 A) modification is the most abundant modification on eukaryotic RNA. In recent years, lots of studies have reported that m 6 A modification and m 6 A RNA methylation regulators were involved in cancer progression. However, the m 6 A level and its regulators in esophageal cancer (ESCA) remain poorly understood. In this study, we analyzed the expression of m 6 A regulators using The Cancer Genome Atlas data and found 14 of 19 m 6 A regulators are significantly increased in ESCA samples. Then we performed a univariate Cox regression analysis and LASSO (least absolute shrinkage and selection operator) Cox regression model to investigate the prognostic role of m 6 A regulators in ESCA, and the results indicated that a two-gene prognostic signature including ALKBH5 and HNRNPA2B1 could predict overall survival of ESCA patients. Moreover, HNRNPA2B1 is higher expressed in high-risk scores subtype of ESCA, indicating that HNRNPA2B1 may be involved in ESCA development. Subsequently, we confirmed that the level of m 6 A and HNRNPA2B1 was significantly increased in ESCA. We also found that HNRNPA2B1 expression positively correlated with tumor diameter and lymphatic metastasis of ESCA. Moreover, functional study showed that knockdown of HNRNPA2B1 inhibited the proliferation, migration, and invasion of ESCA. Mechanistically, we found that knockdown of HNRNPA2B1 inhibited the expression of de novo fatty acid synthetic enzymes, ACLY and ACC1, and subsequently suppressed cellular lipid accumulation. In conclusion, our study provides critical clues to understand the role of m 6 A and its regulators in ESCA. Moreover, HNRNPA2B1 functions as an oncogenic factor in promoting ESCA progression via up-regulation of fatty acid synthesis enzymes ACLY and ACC1, and it may be a promising prognostic biomarker and therapeutic target for human ESCA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Guo

Wang

et al. 2020

Front. Oncol.

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“…LncRNA miR503 host gene (miR503HG) also interacts with HNRNPA2B1 to promote its degradation through an ubiquitin-proteasome pathway in HCC [98]. Similarly, long intergenic non-protein coding RNA 1234 (LINC01234) interacts with HNRNPA2B1 to facilitate cell proliferation and inhibit cell apoptosis in NSCLC [99]. Lin-28 homolog B antisense RNA 1 (LIN28B-AS1) interacts with IGF2BP1 to promote the proliferation and metastasis of lung adenocarcinoma (LUAD) [100].…”

Section: A Regulators Are Regulated By Ncrnas In Cancermentioning

confidence: 99%

Novel insights into the interplay between m6A modification and noncoding RNAs in cancer

et al. 2020

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N6-methyladenosine (m 6 A) is one of the most common RNA modifications in eukaryotes, mainly in messenger RNA (mRNA). Increasing evidence shows that m 6 A methylation modification acts an essential role in various physiological and pathological bioprocesses. Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs and circRNAs, are known to participate in regulating cell differentiation, angiogenesis, immune response, inflammatory response and carcinogenesis. m 6 A regulators, such as METTL3, ALKBH5 and IGF2BP1 have been reported to execute a m 6 Adependent modification of ncRNAs involved in carcinogenesis. Meanwhile, ncRNAs can target or modulate m 6 A regulators to influence cancer development. In this review, we provide an insight into the interplay between m 6 A modification and ncRNAs in cancer.

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“…Pierce Magnetic RNA-Protein Pull-Down Kit (Thermo Fisher Scientific, Waltham, MA) was applied for RNA pull down assay. Protein extracts from GC cell samples were mixed with biotinylated RNAs and beads for 1 h. Thereafter, the eluted proteins from Bio-LINC01559 group were examined by mass spectrometry analysis as previously described 26 .…”

Section: Rna Pull Down Assay and Mass Spectrometrymentioning

confidence: 99%

Exosome-transferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway

Wang

et al. 2020

Cell Death Dis

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Increasing evidence indicates that long non-coding RNAs (lncRNAs) are associated with the progression of human cancers. However, the expression level and function of LINC01559 (long intergenic non-protein coding RNA 1559) in gastric cancer (GC) are rarely reported. Here we found that LINC01559 was upregulated in GC tissues based on GEPIA (Gene Expression Profiling Interactive Analysis) and TCGA (The Cancer Genome Atlas) databases. Also, LINC01559 was expressed at a lower level in GC cells than in mesenchymal stem cells (MSCs). In vitro experiments revealed that silencing LINC01559 remarkably hindered GC cell proliferation, migration and stemness. Then, we identified that LINC01559 was transmitted form MSCs to GC cells via the exosomes. Immunofluorescence staining and electron microscope validated the existence of exosomes in GC cells. Mechanistically, LINC01559 sponged miR-1343-3p to upregulate PGK1 (phosphoglycerate kinase 1), therefore activating PI3K/AKT pathway. Moreover, LINC01559 recruited EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to PTEN (phosphatase and tensin homolog) promoter, inducing the methylation of PTEN promoter and finally resulting in PTEN repression. Of note, LINC01559 targeted both PGK1 and PTEN to promote GC progression by activating PI3K/AKT pathway. Taken together, our study demonstrated that LINC01559 accelerated GC progression via upregulating PGK1 and downregulating PTEN to trigger phosphatidylinositol 3-kinase/AKT serine/threonine kinase (PI3K/AKT) pathway, indicating LINC01559 as a potential biomarker for GC treatment.

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Integrative Analysis of NSCLC Identifies LINC01234 as an Oncogenic lncRNA that Interacts with HNRNPA2B1 and Regulates miR-106b Biogenesis

Cited by 76 publications

References 43 publications

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Novel insights into the interplay between m6A modification and noncoding RNAs in cancer

Exosome-transferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway

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