CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment

Yang, Di; Ma, Jian; Ma, Xiaoxin

doi:10.3389/fcell.2021.721676

Cited by 13 publications

(12 citation statements)

References 40 publications

(37 reference statements)

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“…CDKN2B-AS1 increased NAP1L1 transcription in HCC cells by adsorbing let-7c-5p, which activates the PI3K/AKT/mTOR activity [ 34 ]. Yang et al observed that CDKN2B-AS1 knockdown inhibited endometrial carcinogenesis both in vivo and in vitro, and the tumor size was smaller in the CDKN2B-AS1 knockdown group than in the nonknockdown group [ 35 ]. The current study found that CDKN2B-AS1 is a potential risk for EC.…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related lncRNA for the Establishment of Novel Prognostic Signature and Therapeutic Response Prediction to Endometrial Carcinoma

Zhou

Dai

et al. 2022

BioMed Research International

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Background. Ferroptosis is a recently described form of intentional cellular damage that is iron-dependent and separate from apoptosis, cellular necrosis, and autophagy. It has been demonstrated to be adequately regulated by long noncoding RNAs (lncRNAs) in various cancers. However, the predictive profile of ferroptosis-related lncRNAs (FRLs) in endometrial carcinoma (EC) is unknown. Herein, FRLs associated with uterine corpus endometrial carcinoma (UCEC) prognosis were screened to predict treatment response in EC. Methods. Samples of EC and adjacent normal tissues were obtained from The Cancer Genome Atlas (TCGA) dataset repository. Limma and survival packages in R software were used to screen FRLs associated with the prognosis of EC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) chord and circle plots of FRLs were also plotted. Next, FRLs screened by the least absolute shrinkage and selection operator (LASSO) method were applied to construct and validate a multivariate Cox proportional risk regression model. Nomogram plots were created to forecast the outcome of UCEC patients, and gene set enrichment analysis (GSEA), principal component analysis (PCA), and immunoassays were performed on the prognostic models. Finally, limma, ggpubr, pRRophetic, and ggplot2 programs were used for drug sensitivity analysis of the prognostic models. Results. A signature based on nine FRLs (CFAP58-DT, LINC00443, EMSLR, HYI-AS1, ADIRF-AS1, LINC02474, CDKN2B-AS1, LINC01629, and LINC00942) was constructed. The developed FRL prognostic model effectively discriminated UCEC patients into low-risk and high-risk groups. Immunological checkpoints CD80 and CD40 were strongly expressed in the high-risk group. In addition, the nine FRLs were all more expressed in the high-risk group compared to the low-risk group. Conclusion. These findings significantly contribute to the understanding of the function of FRLs in UCEC and provide promising therapeutic strategies for UCEC.

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Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related lncRNA for the Establishment of Novel Prognostic Signature and Therapeutic Response Prediction to Endometrial Carcinoma

Zhou

Dai

et al. 2022

BioMed Research International

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“…By combining the results of this experiment with previous related studies [27,31,32], we believe that CDKN2B-AS1 and miR-199a-5p can be used as clinical routine screening indicators, so as to improve the early diagnosis rate of LC and provide relevant treatment for patients in a timely manner. What is more, CDKN2B-AS1 with miR-199a-5p can be used as an indicator of disease progression in LC to aid clinical understanding of disease progression.…”

Section: Discussionmentioning

confidence: 57%

Significance of lncRNA CDKN2B-AS1 in Interventional Therapy of Liver Cancer and the Mechanism under Its Participation in Tumour Cell Growth via miR-199a-5p

Pan

et al. 2022

Journal of Oncology

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Background and Objective. This research probed the function of lncRNA CDKN2B-AS1 (CDKN2B-AS1) in interventional therapy of liver cancer (LC) and its association with miR-199a-5p, to offer more comprehensive and reliable references for future diagnosis and therapy. Methods. Totally 34 LC patients admitted to our hospital between January 2020 and March 2021 (Obs group) and 32 healthy individuals over the same time span (Con group) were enrolled. CDKN2B-AS1 and miR-199a-5p in the two groups were PCR quantified, and their association and value for the diagnosis and therapy of LC were analyzed. In addition, purchased LC cells were adopted for in vitro assays, and the influences of CDKN2B-AS1 and miR-199a-5p on biological behaviours of LC cells were assessed through CCK-8, Transwell, and flow cytometry experiment, and their regulatory association was verified by the dual luciferase reporter (DLR) assay and rescue assay. And the autophagic protein expression was tested by the western blot to confirm the effect of both on the autophagic capacity of LC cells. Results. CDKN2B-AS1 in LC cases presented high expression and dropped after therapy ( P < 0.05 ), and the opposite situation of miR-199a-5p was found in the LC cases ( P < 0.05 ). In vitro assays, after silencing of CDKN2B-AS1 and upregulation of miR-199a-5p, LC cells presented weaker viability, invasion and migration activities, and stronger apoptotic activity (all P < 0.05 ). The DLR assay revealed suppressed fluorescence activity of CDKN2B-AS1-WT by miR-199a-5p ( P < 0.05 ). Moreover, according to the rescue assay, the impacts of silencing CDKN2B-AS1 on LC cells could be completely offset by silencing miR-199a-5p ( P < 0.05 ). According to the clone formation and WB assay, the growth and autophagy of LC cells were under the regulation of CDKN2B-AS1 targeting miR-199a-5p ( P < 0.05 ). Conclusion. With high expression in LC cases, CDKN2B-AS1 is implicated in the development and progression of LC by suppressing cell autophagy through targeting miR-199a-5p.

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“…AUC of the risk model was 0.687, which is not as good as ours (AUC = 0.718 for 5‐year survival). 28 These studies including ours all suggested that LNM‐related genes were promising for many types of cancer in the prediction of overall survival.…”

Section: Discussionmentioning

confidence: 71%

Construction and validation of a prognostic model based on 11 lymph node metastasis‐related genes for overall survival in endometrial cancer

Feng

Miao

et al. 2022

Cancer Medicine

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Background: Endometrial cancer (EC) is one of the most common malignant tumor in the female reproductive system. The incidence of lymph node metastasis (LNM) is only about 10% in clinically suspected early-stage EC patients. Discovering prognostic model and effective biomarkers for early diagnosis is important to reduce the mortality rate.Methods: We downloaded the RNA-sequencing data and clinical information from the TCGA database. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the differentially expressed genes (DEGs). A least absolute shrinkage and selection operator (LASSO) regression was conducted to identify the characteristic dimension decrease and distinguish prognosis-related LNM related genes signature. Subsequently, a novel prognosis-related nomogram to predict overall survival (OS). A survival analysis was carried out to explore the individual prognostic signi cance of the risk model and key gene was validated in vitro.Results: In total, 89 LRGs were identi ed. Based on the LASSO Cox regression, 11 genes were selected for the development of a risk evaluation model. The Kaplan-Meier curve indicated that patients in the lowrisk group had considerably better OS (P = 3.583e−08). The area under the curve (AUC) of this model was 0.718 at 5 years of OS. Then, we developed an OS-associated nomogram that included the risk score and clinicopathological features. The concordance index of the nomogram was 0.769. The survival veri cation performed in three subgroups from the nomogram demonstrated the validity of the model.The AUC of the nomogram was 0.787 at 5 years OS. Proliferation and metastasis of HMGB3 were explored in EC cell line. Finally, we revealed that the most frequently mutated genes in the low-risk and high-risk groups are PTEN and TP53, respectively. Conclusions: Our results suggest that LNM plays an important role in the prognosis, and HMGB3 was potential as a biomarker for EC patients. By detecting the mutation of the risk signature, clinicians can accurately treat patients with targeted therapy, thereby improving their survival rate.

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CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment

Cited by 13 publications

References 40 publications

Ferroptosis-Related lncRNA for the Establishment of Novel Prognostic Signature and Therapeutic Response Prediction to Endometrial Carcinoma

Ferroptosis-Related lncRNA for the Establishment of Novel Prognostic Signature and Therapeutic Response Prediction to Endometrial Carcinoma

Significance of lncRNA CDKN2B-AS1 in Interventional Therapy of Liver Cancer and the Mechanism under Its Participation in Tumour Cell Growth via miR-199a-5p

Construction and validation of a prognostic model based on 11 lymph node metastasis‐related genes for overall survival in endometrial cancer

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