A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability

Zhu, Peng; He, Fang; Hou, Yixuan; Tu, Gang; Li, Qiao; Jin, Tengchuan; Zeng, Hualin; Qin, Yilu; Wan, Xueying; Qiao, Yina; Qiu, Yumin; Teng, Yong; Liu, Manran

doi:10.1038/s41388-020-01638-9

Cited by 155 publications

(121 citation statements)

References 69 publications

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“…Indeed, RNF144A-AS1 could cooperate with EIF2AK2 to inhibit the expression of IFN-γ revealed by Huynh et al [ 36 ]. Similarly, in GC, RNF144A-AS1 may interact with RNA-binding protein to influence gene expression or act as a cofactor for transcriptional factors and chromatin modifiers to participate in gene regulation, considering the portion of nuclear localization of it [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

RNF144A-AS1, a TGF-β1- and hypoxia-inducible gene that promotes tumor metastasis and proliferation via targeting the miR-30c-2-3p/LOX axis in gastric cancer

Shi

et al. 2021

Cell Biosci

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Background Although recent molecular analyses have improved our knowledge regarding gastric cancer (GC) biology, the molecular mechanisms that confer metastatic potential to GC remain poorly understood. In this study, we intend to explore the function and characterize the underlying mechanism of long noncoding RNA RNF144A-AS1 in GC metastasis and outgrowth. Methods The expression of RNF144A-AS1, miR-30c-2-3p, and Lysyl oxidase (LOX) was detected by quantitative real-time PCR assay. Fluorescence in situ hybridization and subcellular fractionation assay determined the cellular localization of RNF144A-AS1. Cell counting kit 8 assay, transwell assay, and tube formation assay were performed to detect the effect on cell proliferation, migration, invasion, and angiogenesis, respectively. Animal models were also applied to verify the effect on tumor metastasis, outgrowth, and angiogenesis. Bioinformatic analysis, luciferase reporter assay, and RNA immunoprecipitation (RIP) assay explored the interactions among RNF144A-AS1, miR-30c-2-3p, and LOX. Gene regulation was further validated by knockdown of Dicer or mutating the miRNA binding sites on RNF144A-AS1 and LOX 3ʹUTR. Cells were treated with recombinant human TGF-β1 (Transforming Growth Factor β1) to explore the effect of TGF-β1 on RNF144A-AS1. Western blot and immunohistochemistry were used to detect protein expression. Results The expression of RNF144A-AS1 was significantly upregulated in GC tissues and was associated with poor prognosis and later-stage diseases. Hypoxia stimulated the expression of RNF144A-AS1 in a HIF-1α-independent manner. Additionally, RNF144A-AS1 was also induced by TGF-β1. Loss and gain of function assays revealed that RNF144A-AS1 promoted tumor metastasis, angiogenesis, and proliferation. Mechanism exploration indicated RNF144A-AS1 served as a microRNA decoy of miR-30c-2-3p to release LOX. Gene Set Enrichment Analysis further suggested LOX and RNF144A-AS1 were enriched in the same gene sets, emphasizing the internal mechanism connection between these two genes. Conclusions TGF-β1- and hypoxia-inducible RNF144A-AS1 promoted tumor metastasis, angiogenesis, and proliferation through targeting the miR-30c-2-3p/LOX axis in GC, highlighting the value of the RNF144A-AS1/miR-30c-2-3p/LOX axis in therapeutic interventions of GC.

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Section: Discussionmentioning

confidence: 99%

RNF144A-AS1, a TGF-β1- and hypoxia-inducible gene that promotes tumor metastasis and proliferation via targeting the miR-30c-2-3p/LOX axis in gastric cancer

Shi

et al. 2021

Cell Biosci

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“…For instance, LINC00958 regulated by m6a modification can promote breast cancer tumorigenesis through miR-378a-3p and YY1 axis ( Rong et al, 2021 ). A novel hypoxic long-stranded noncoding RNA KB-1980E6.3 maintains stemness in breast cancer stem cells by interacting with IGF2BP1 to promote the stability of c-Myc mRNA ( Zhu et al, 2021 ). MALAT1 promotes thyroid cancer progression by binding to miR-204 and upregulating IGF2BP2, thereby affecting miR-204/IGF2BP2/m6A-MYC signaling ( Ye et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

m6A-Related lncRNAs Are Potential Biomarkers for the Prognosis of Metastatic Skin Cutaneous Melanoma

Huang

Lyu

Gao

et al. 2021

Front. Mol. Biosci.

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Background: The incidence of skin cutaneous melanoma (SKCM) has risen more rapidly than any other solid tumor in the past few decades. The median survival for metastatic melanoma is only six to nine months and the 5°years survival rate of patients with conventional therapy is less than 5%. Our aim was to reveal the potential molecular mechanism in m6A modification of lncRNA and provide candidate prognostic biomarkers for metastatic SKCM.Methods: lncRNAs expression level was obtained by re-annotation in TCGA and CCLE datasets. m6A-related lncRNAs were selected though correlation analysis. Univariate cox regression analysis was used to screen out independent prognostic factors. LASSO Cox regression was performed to construct an m6A-related lncRNA model (m6A-LncM). Univariate survival analysis and ROC curve were used to assess the prognostic efficacy of this model and candidate lncRNAs. Enrichment analysis was used to explore the candidate genes’ functions.Results: We obtained 1,086 common m6A-related lncRNAs after Pearson correlation analysis in both two datasets. 130 out of the 1,086 lncRNAs are independent prognostic factors. 24 crucial lncRNAs were filtered after LASSO Cox regression analysis. All the m6A-LncM and the 24 lncRNAs were related to overall survival. Stratified survival analysis of m6A-LncM showed that the model retains its prognostic efficacy in recurrence, radiation therapy and other subgroups. Enrichment analysis also found that these lncRNAs were immune associated.Conclusion: Here, we obtained 24 crucial lncRNAs that may be potential biomarkers to predict survival of metastatic SKCM and may provide a new insight to improve the prognosis of it.

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“…It has also been reported that m6A modification can stabilize and promote the expression of MYC through the IGF2BP pathway [5,49,76], or by stabilizing AFF4, maintaining the transcription of MYC and affecting cell proliferation [77]. Interestingly, lncRNA KB-1980E6.3 can bind to the recognition protein IGF2BP1 to synergistically stabilize c-Myc mRNA [78]. In addition to MYC, the well-known tumor suppressor gene PTEN is also regulated by m6A modification.…”

Section: N6-methyladenosine Can Be Associated With Cancer Cell Proliferationmentioning

confidence: 99%

N6-methyladenosine-dependent signalling in cancer progression and insights into cancer therapies

Tan

Zhao

Xiong

et al. 2021

J Exp Clin Cancer Res

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The N6-methyladenosine (m6A) modification is a dynamic and reversible epigenetic modification, which is co-transcriptionally deposited by a methyltransferase complex, removed by a demethylase, and recognized by reader proteins. Mechanistically, m6A modification regulates the expression levels of mRNA and nocoding RNA by modulating the fate of modified RNA molecules, such as RNA splicing, nuclear transport, translation, and stability. Several studies have shown that m6A modification is dysregulated in the progression of multiple diseases, especially human tumors. We emphasized that the dysregulation of m6A modification affects different signal transduction pathways and involves in the biological processes underlying tumor cell proliferation, apoptosis, invasion and migration, and metabolic reprogramming, and discuss the effects on different cancer treatment.

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A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability

Cited by 155 publications

References 69 publications

RNF144A-AS1, a TGF-β1- and hypoxia-inducible gene that promotes tumor metastasis and proliferation via targeting the miR-30c-2-3p/LOX axis in gastric cancer

RNF144A-AS1, a TGF-β1- and hypoxia-inducible gene that promotes tumor metastasis and proliferation via targeting the miR-30c-2-3p/LOX axis in gastric cancer

m6A-Related lncRNAs Are Potential Biomarkers for the Prognosis of Metastatic Skin Cutaneous Melanoma

N6-methyladenosine-dependent signalling in cancer progression and insights into cancer therapies

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