SNP-mediated lncRNA-ENTPD3-AS1 upregulation suppresses renal cell carcinoma via miR-155/HIF-1α signaling

Wang, Jiangyi; Zou, Yun; Du, Bowen; Li, Wenzhi; Yu, Guopeng; Li, Long; Zhou, Lin; Gu, Xin; Shi, Song; Liu, Yushan; Zhou, Wenquan; Xu, Bin; Wang, Zhong

doi:10.1038/s41419-021-03958-4

Cited by 36 publications

(25 citation statements)

References 38 publications

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“…MYOSLID was involved in the growth of osteosarcoma and amplifies the vascular smooth muscle differentiation program [ 37 , 38 ]. ENTPD3-AS1 could suppress renal cancer via miR-155/HIF-1 signaling, which confirmed our results [ 39 ]. Overall, referred to former researches, we observed that the necroptosis-related risk lncRNAs identified in our study are strongly associated with immune functions.…”

Section: Discussionsupporting

confidence: 92%

Qualification of Necroptosis-Related lncRNA to Forecast the Treatment Outcome, Immune Response, and Therapeutic Effect of Kidney Renal Clear Cell Carcinoma

Yin

Tian

Ren

et al. 2022

Journal of Oncology

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Background. Kidney renal clear cell carcinoma (KIRC) is considered as a highly immune infiltrative tumor. Necroptosis is an inflammatory programmed cell death associated with a wide range of diseases. Long noncoding RNAs (lncRNAs) play important roles in gene regulation and immune function. lncRNA associated with necroptosis could systematically explore the prognostic value, regulate tumor microenvironment (TME), etc. Method. The patients’ data was collected from TCGA datasets. We used the univariate Cox regression (UCR) to select prediction lncRNAs that are related to necroptosis. Meanwhile, risk models were constructed using LASSO Cox regression (LCR). Kaplan–Meier (KM) analysis, accompanied with receiver operating characteristic (ROC) curves, was performed to assess the independent risk factors of different clinical characteristics. The evaluated factors are age, gender, disease staging, grade, and their related risk score. Databases such as Gene Ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Gene set enrichment analysis (GSEA) were used to search the probable biological characteristics that could influence the risk groups, containing signaling pathway and immue-related pathways. The single-sample gene set enrichment analysis (ssGSEA) was chosen to perform gene set variation analysis (GSVA), and the GSEABase package was selected to detect the immune and inflammatory infiltration profiles. The TIDE and I C 50 evaluation were used to estimate the effectiveness of clinical treatment on KIRC. Results. Based on the above analysis, we have got a conclusion that patients who show high risk had higher immune infiltration, immune checkpoint expression, and poorer prognosis. We identified 19 novel prognostic necroptosis-related lncRNAs, which could offer opinions for a deeper study of KIRC. Conclusion. The risk model we constructed makes it possible to predict the prognosis of KIRC patients and offers directions for further research on the prognostication and treatment strategies for KIRC.

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Section: Discussionsupporting

confidence: 92%

Qualification of Necroptosis-Related lncRNA to Forecast the Treatment Outcome, Immune Response, and Therapeutic Effect of Kidney Renal Clear Cell Carcinoma

Yin

Tian

Ren

et al. 2022

Journal of Oncology

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“…Recently, several studies revealed that functional variations in lncRNAs can influence cancer susceptibility by changing the expression of lncRNAs 31–33 . For instance, they can cause the host gene dysregulation by gaining or losing miRNA‐binding sites due to the secondary structure alteration 34,35 …”

Section: Introductionmentioning

confidence: 99%

“…[31][32][33] For instance, they can cause the host gene dysregulation by gaining or losing miRNA-binding sites due to the secondary structure alteration. 34,35 LINC01614, a two-exon lncRNA that maps to chromosome 2q35, was initially identified to be upregulated in lung cancer. 36 Recent studies showed that LINC01614 was associated with the development and progression of breast cancer and gastric cancer through distinct molecular mechanisms.…”

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confidence: 99%

Risk SNP‐mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway

Hou

Zhou

et al. 2022

Molecular Carcinogenesis

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As potential biomarkers and therapeutic targets, long noncoding RNAs (lncRNAs) are involved in the tumorigenesis of various tumors. Genetic variation in long noncoding regions can lead to lncRNA dysfunction and even cancer. Nevertheless, studies on the association between lncRNA‐associated single‐nucleotide polymorphisms (SNPs) and the risk of head and neck squamous cell carcinoma (HNSCC) remain inadequate. Here, we aimed to explore the association between SNPs in LINC01614 and HNSCC risk, and the potential role of LINC01614 in tumorigenesis. In this study, we found that rs16854802 A > G (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.22–1.77, p < 0.001) and rs3113503 G > C (OR = 1.38, 95% CI: 1.15–1.64, p < 0.001) in LINC01614 increased the risk of HNSCC in the Chinese population. Functional bioinformatic analysis and luciferase reporter assay revealed that rs3113503 G > C variant disrupted the binding of miRNA‐616‐3p to LINC01614, which resulted in the increased expression of LINC01614. Further analysis of the TCGA database demonstrated that the upregulated LINC01614 in HNSCC cancer tissues was associated with poor prognostic in HNSCC patients. In vitro experiments showed that knockdown of LINC01614 inhibited the proliferation, invasion, and migration ability of HNSCC cells. Mechanistically, allele C of rs3113503 in LINC01614 was more effective than allele G in activating the PI3K/AKT signaling pathway. Moreover, the reduced expression of LINC01614 also inhibited the activation of the PI3K/AKT signaling pathway. In summary, our findings revealed that the risk SNP rs3113503 G > C in LINC01614 altered the binding to miR‐616‐3p, which led to increased LINC01614 expression and promoted HNSCC progression by activating the PI3K/AKT signaling pathway.

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“…The five other novel signals localized to ENTPD3/ENTPD3-AS1 (a tumor suppressor ( Li M. et al, 2019 ) that strongly signals through HIF1 ( Wang J. et al, 2021 ) and its associated antisense RNA) , NCK2 [a critical immune adaptor protein linking B-cell receptor activation to PI3K signaling ( Cannons et al, 2013 )], IFLTD1 [a ciliary organization protein and cancer risk gene ( Wang et al, 2005 ), also known as LMNTD1 and PAS1C1 ], AGXT2 [a risk locus of premature myocardial infarct ( Yuanfeng et al, 2016 )], DOCK10 [critical in B-cell activation and proliferation ( Yelo et al, 2008 )], and the microRNA MIR548AG1 .…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study for systemic lupus erythematosus in an egyptian population

Elghzaly

Sun²,

Looger³

et al. 2022

Front. Genet.

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Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians–an admixed North African/Middle Eastern population–using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10−8) and eight novel suggestive loci (Pcorrected < 1.0 × 10−5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10−95 < p < 1.0 × 10−2) across diverse tissues. These loci are involved in cellular proliferation and invasion—pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.

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SNP-mediated lncRNA-ENTPD3-AS1 upregulation suppresses renal cell carcinoma via miR-155/HIF-1α signaling

Cited by 36 publications

References 38 publications

Qualification of Necroptosis-Related lncRNA to Forecast the Treatment Outcome, Immune Response, and Therapeutic Effect of Kidney Renal Clear Cell Carcinoma

Qualification of Necroptosis-Related lncRNA to Forecast the Treatment Outcome, Immune Response, and Therapeutic Effect of Kidney Renal Clear Cell Carcinoma

Risk SNP‐mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway

Genome-wide association study for systemic lupus erythematosus in an egyptian population

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