Regulation of melanoma malignancy by the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis

Chen, Xiangjun; Li, Sha; Han, Dongmei; Han, Dezhi; Sun, Weijing; Zhao, Xiaochun

doi:10.1038/s41417-020-00274-5

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…There is considerable evidence that lncRNAs provide an additional degree of complexity to the regulation of genes, including several famous OIS-related genes like INK4A ( Montes et al, 2015 ), KRAS ( La Montagna et al, 2021 ), NRAS ( Chen et al, 2021 ) and PTEN ( Zang et al, 2020 ). Given the prognostic risk of OIS in HCC and the pivotal roles of lncRNAs in cellular senescence ( Abdelmohsen and Gorospe, 2015 ), we therefore went on to identify the OIS-related lncRNAs in HCC.…”

Section: Resultsmentioning

confidence: 99%

Identification of senescence-associated long non-coding RNAs to predict prognosis and immune microenvironment in patients with hepatocellular carcinoma

Gao

Zhou²,

Cheng³

et al. 2022

Front. Genet.

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Background: Cellular senescence plays a complicated and vital role in cancer development because of its divergent effects on tumorigenicity. However, the long non-coding RNAs (lncRNAs) associated with tumor senescence and their prognostic value in hepatocellular carcinoma (HCC) remain unexplored.Methods: The trans-cancer oncogene-induced senescence (OIS) signature was determined by gene set variation analysis (GSVA) in the cancer genome atlas (TCGA) dataset. The OIS-related lncRNAs were identified by correlation analyses. Cox regression analyses were used to screen lncRNAs associated with prognosis, and an optimal predictive model was created by regression analysis of the least absolute shrinkage and selection operator (LASSO). The performance of the model was evaluated by Kaplan-Meier survival analyses, nomograms, stratified survival analyses, and receiver operating characteristic curve (ROC) analyses. Gene set enrichment analysis (GSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) were carried out to explore the functional relevance and immune cell infiltration, respectively.Results: Firstly, we examined the pan-cancer OIS signature, and found several types of cancer with OIS strongly associated with the survival of patients, including HCC. Subsequently, based on the OIS signature, we identified 76 OIS-related lncRNAs with prognostic values in HCC. We then established an optimal prognostic model based on 11 (including NRAV, AC015908.3, MIR100HG, AL365203.2, AC009005.1, SNHG3, LINC01138, AC090192.2, AC008622.2, AL139423.1, and AC026356.1) of these lncRNAs by LASSO-Cox regression analysis. It was then confirmed that the risk score was an independent and potential risk indicator for overall survival (OS) (HR [95% CI] = 4.90 [2.74–8.70], p < 0.001), which outperforms those traditional clinicopathological factors. Furthermore, patients with higher risk scores also showed more advanced levels of a proinflammatory senescence-associated secretory phenotype (SASP), higher infiltration of regulatory T (Treg) cells and lower infiltration of naïve B cells, suggesting the regulatory effects of OIS on immune microenvironment. Additionally, we identified NRAV as a representative OIS-related lncRNA, which is over-expressed in HCC tumors mainly driven by DNA hypomethylation.Conclusion: Based on 11 OIS-related lncRNAs, we established a promising prognostic predictor for HCC patients, and highlighted the potential immune microenvironment-modulatory roles of OIS in HCC, providing a broad molecular perspective of tumor senescence.

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Section: Resultsmentioning

confidence: 99%

Identification of senescence-associated long non-coding RNAs to predict prognosis and immune microenvironment in patients with hepatocellular carcinoma

Gao

Zhou²,

Cheng³

et al. 2022

Front. Genet.

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“…Among the 5 downregulated miRs in vaginal melanoma, miR-145-5p has been shown to function as a tumor suppressor miR in cutaneous melanoma via inhibition of TLR4 and NRAS expression and subsequent regulation of the downstream NF-κB and MAPK signaling pathways that contribute to tumor proliferation, migration, and invasion [ 45 , 46 ]. There were 14 significantly upregulated miRs in vaginal melanoma and miR-106a-5p, miR-17-5p, and miR-20b-5p displayed the greatest fold change.…”

Section: Discussionmentioning

confidence: 99%

“…expression and subsequent regulation of the downstream NF-κB and MAPK signaling pathways that contribute to tumor proliferation, migration, and invasion [45,46]. There were 14 significantly upregulated miRs in vaginal melanoma and miR-106a-5p, miR-17-5p, and miR-20b-5p displayed the greatest fold change.…”

Section: Plos Onementioning

confidence: 99%

Expression of microRNAs and their target genes in melanomas originating from gynecologic sites

et al. 2023

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Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that MOGS would display unique miR and mRNA expression profiles. The miR and mRNA expression profile in RNA from formalin fixed, paraffin embedded vaginal melanomas (relative to vaginal mucosa) and vulvar melanomas (relative to cutaneous melanoma) were measured with the Nanostring Human miRNA assay and Tumor Signaling mRNA assay. Differential patterns of expression were identified for 21 miRs in vaginal and 47 miRs in vulvar melanoma (fold change >2, p<0.01). In vaginal melanoma, miR-145-5p (tumor suppressor targeting TLR4, NRAS) was downregulated and miR-106a-5p, miR-17-5p, miR-20b-5p (members of miR-17-92 cluster) were upregulated. In vulvar melanoma, known tumor suppressors miR-200b-3p and miR-200a-3p were downregulated, and miR-20a-5p and miR-19b-3p, from the miR-17-92 cluster, were upregulated. Pathway analysis showed an enrichment of “proteoglycans in cancer”. Among differentially expressed mRNAs, topoisomerase IIα (TOP2A) was upregulated in both MOGS. Gene targets of dysregulated miRs were identified using publicly available databases and Pearson correlations. In vaginal melanoma, suppressor of cytokine signaling 3 (SOCS3) was downregulated, was a validated target of miR-19b-3p and miR-20a-5p and trended toward a significant inverse Pearson correlation with miR-19b-3p (p = 0.093). In vulvar melanoma, cyclin dependent kinase inhibitor 1A (CDKN1A) was downregulated, was the validated target of 22 upregulated miRs, and had a significant inverse Pearson correlation with miR-503-5p, miR-130a-3p, and miR-20a-5p (0.005 < p < 0.026). These findings support microRNAs as mediators of gene expression in MOGS.

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“…As reported by Global Cancer Statistics, there were approximately 325 000 new reported melanoma cases and 57 000 melanoma death cases in 2020 [1]. In the 40 years that have passed, the incidence and fatality rate of melanoma have been increasing [2]. It is responsible for 1.7% of all new diagnoses of primary malignancies per year [3].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a nomogram for elderly patients with ulcerative melanoma

Yan,

Wang,

et al. 2023

Melanoma Research

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The current state of survival prediction models for elderly patients with ulcerative melanoma (uCM) is limited. We sought to develop a nomogram model that can predict overall survival of geriatric patients with uCM. The Surveillance, Epidemiology, and End Results (SEER) database served as a source for patients diagnosed with uCM between 2004 and 2015. Statistical analyses were conducted to determine the significant prognostic elements affecting overall survival using multivariate and univariate Cox proportional risk regression models. Subsequently, an independent forecasting nomogram was developed on the basis of these identified predictors. The predictive model was then assessed and validated through the utilization of receiver operating characteristic curves, calibration curves as well as decision curves. The study included a total of 5019 participants. Univariate and multivariate analyses revealed age, sex, marital status, primary site, tumor size, N stage, M stage, histological type, and surgery were independent prognostic factors. A nomogram was developed using the findings from both univariate and multivariate Cox analyses (P < 0.05). The receiver operating characteristic curves, which vary over time, and the area under the curve (AUC) for the training and validation cohorts, demonstrated the nomogram’s strong discriminatory ability. Additionally, the calibration curves indicated satisfactory agreement between the predicted values from the nomogram and the practical outcomes observed in both cohorts. Furthermore, the decision curve analysis curves displayed favorable positive net gains at all times, when the critical value is most likely to occur. In this study, age, sex, marital status, primary site, tumor size, N stage, M stage, histologic type and surgery were determined as independent predictors for elderly patients with uCM. Then, a predictive model with good discriminatory ability was constructed to predict 12-, 24-, and 36-month overall survival in geriatric patients with uCM, which facilitates patients’ counseling and individualized medical decision.

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Regulation of melanoma malignancy by the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis

Cited by 4 publications

References 42 publications

Identification of senescence-associated long non-coding RNAs to predict prognosis and immune microenvironment in patients with hepatocellular carcinoma

Identification of senescence-associated long non-coding RNAs to predict prognosis and immune microenvironment in patients with hepatocellular carcinoma

Expression of microRNAs and their target genes in melanomas originating from gynecologic sites

Development and validation of a nomogram for elderly patients with ulcerative melanoma

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