The Interplay between Long Noncoding RNAs and Proteins of the Epigenetic Machinery in Ovarian Cancer

Calanca, Naiade; Abildgaard, Cecilie; Rainho, Cláudia Aparecida; Rogatto, Sílvia Regina

doi:10.3390/cancers12092701

Cited by 6 publications

(4 citation statements)

References 144 publications

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“…Accumulating studies have demonstrated that lncRNA is implicated in a variety of biological processes and is closely associated with tumor development [13,15,18,19,27,37,38]. LncRNAs also show fine potential in clinical molecular diagnosis in various types of cancers [18,19].…”

Section: Discussionmentioning

confidence: 99%

Elevated LINC00909 Promotes Tumor Progression of Ovarian Cancer via Regulating the miR-23b-3p/MRC2 Axis

Yang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ovarian cancer (OC), the third common gynecologic malignancy, contributes to the most cancer-caused mortality in women. However, 70% of patients with OC are diagnosed at an advanced stage, of which the 5-year survival is less than 30%. Long noncoding RNAs (long ncRNAs or lncRNA), a type of RNA with exceeding 200 nucleotides in length but no protein-coding capability, have been demonstrated to involve the pathogenesis of various cancers and show considerable potential in the diagnosis of OC. In this study, we found that the LINC00909 expression in tumor and serum specimens of OC patients was elevated, determined by real-time quantitative, and droplet digital PCR. In receiver operating characteristic (ROC) analysis, our results revealed that serum LINC00909 distinguished cancers from normal ovarian tissue with 87.8% of sensitivity and 69.6% of specificity (AUC, 81.2%) and distinguished serous ovarian cancer from normal ovarian tissue with 90.0% of sensitivity and 75.9% of specificity (AUC, 84.5%). Furthermore, we observed that the tumor and serum LINC00909 level was positively associated with the International Federation of Gynecology and Obstetrics (FIGO) stage and the Eastern Cooperative Oncology Group (ECOG) score (reflecting patients’ performance status). Also, patients with low serum LINC00909 level showed a longer overall (hazard ratio, HR = 1.874 , p = 0.0004 ) and progression-free ( HR = 1.656 , p = 0.0017 ) survival. Functional assays indicated that the elevation of LINC00909 expression contributes to cell proliferation, migration, and invasion capability of ovarian cancer cells. Besides, we demonstrated that LINC00909 functions as a competing endogenous RNA (ceRNA) of MRC2 mRNA by sponging miR-23-3p, and thereby promotes epithelial-to-mesenchymal transition (EMT) of ovarian cancer cells. Therefore, we highlight that the LINC00909/miR-23b-3p/MRC2 axis is implicated in the pathogenesis of ovarian cancer, and serum LINC00909 may be a promising biomarker for the diagnosis of OC.

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Section: Discussionmentioning

confidence: 99%

Elevated LINC00909 Promotes Tumor Progression of Ovarian Cancer via Regulating the miR-23b-3p/MRC2 Axis

Yang

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Long non-coding RNAs (lncRNAs) are recognized as key players in epigenetic regulation among patients with cancer ( 15 ), including patients with OC ( 16 ). However, few studies have focused on the role of lncRNAs in the pyroptosis of OC.…”

Section: Discussionmentioning

confidence: 99%

Role of a Pyroptosis-Related lncRNA Signature in Risk Stratification and Immunotherapy of Ovarian Cancer

Zhang

Yan

2022

Front. Med.

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Background: Pyroptosis is a newly recognized form of cell death. Emerging evidence has suggested the crucial role of long non-coding RNAs (lncRNAs) in the tumorigenesis and progression of ovarian cancer (OC). However, there is still poor understanding of pyroptosis-related lncRNAs in OC.Methods: The TCGA database was accessed for gene expression and clinical data of 377 patients with OC. Two cohorts for training and validation were established by random allocation. Correlation analysis and Cox regression analysis were performed to identify pyroptosis-related lncRNAs and construct a risk model.Results: Six pyroptosis-related lncRNAs were included in the final signature with unfavorable survival data. Subsequent ROC curves showed promising predictive value of patient prognosis. Further multivariate regression analyses confirmed the signature as an independent risk factor in the training (HR: 2.242, 95% CI: 1.598–3.145) and validation (HR: 1.884, 95% CI: 1.204–2.95) cohorts. A signature-based nomogram was also established with a C-index of.684 (95% CI: 0.662–0.705). Involvement of the identified signature in multiple immune-related pathways was revealed by functional analysis. Moreover, the signature was also associated with higher expression of three immune checkpoints (PD-1, B7-H3, and VSIR), suggesting the potential of the signature as an indicator for OC immunotherapies.Conclusion: This study suggests that the identified pyroptosis-related lncRNA signature and signature-based nomogram may serve as methods for risk stratification of OC. The signature is also associated with the tumor immune microenvironment, potentially providing an indicator for patient selection of immunotherapy in OC.

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“…In a platinum-sensitive OC cohort mostly comprised of patients with HGSC, the combination of CAMK2N1 (calcium/calmodulin dependent protein kinase II inhibitor 1) and RUNX3 (RUNX family transcription factor 3) methylation in tumor specimens was associated with shorter OS and PFS [ 57 ]. Additionally, dysregulated DNA methylation may interfere with the expression of lncRNAs in OC, disrupting many processes, including tumor suppressive and oncogenic activities [ 58 , 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

The Long Non-Coding RNA SNHG12 as a Mediator of Carboplatin Resistance in Ovarian Cancer via Epigenetic Mechanisms

Abildgaard

Canto

Rainho

et al. 2022

Cancers

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Genetic and epigenetic changes contribute to intratumor heterogeneity and chemotherapy resistance in several tumor types. LncRNAs have been implicated, directly or indirectly, in the epigenetic regulation of gene expression. We investigated lncRNAs that potentially mediate carboplatin-resistance of cell subpopulations, influencing the progression of ovarian cancer (OC). Four carboplatin-sensitive OC cell lines (IGROV1, OVCAR3, OVCAR4, and OVCAR5), their derivative resistant cells, and two inherently carboplatin-resistant cell lines (OVCAR8 and Ovc316) were subjected to RNA sequencing and global DNA methylation analysis. Integrative and cross-validation analyses were performed using external (The Cancer Genome Atlas, TCGA dataset, n = 111 OC samples) and internal datasets (n = 39 OC samples) to identify lncRNA candidates. A total of 4255 differentially expressed genes (DEGs) and 14529 differentially methylated CpG positions (DMPs) were identified comparing sensitive and resistant OC cell lines. The comparison of DEGs between OC cell lines and TCGA-OC dataset revealed 570 genes, including 50 lncRNAs, associated with carboplatin resistance. Eleven lncRNAs showed DMPs, including the SNHG12. Knockdown of SNHG12 in Ovc316 and OVCAR8 cells increased their sensitivity to carboplatin. The results suggest that the lncRNA SNHG12 contributes to carboplatin resistance in OC and is a potential therapeutic target. We demonstrated that SNHG12 is functionally related to epigenetic mechanisms.

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The Interplay between Long Noncoding RNAs and Proteins of the Epigenetic Machinery in Ovarian Cancer

Cited by 6 publications

References 144 publications

Elevated LINC00909 Promotes Tumor Progression of Ovarian Cancer via Regulating the miR-23b-3p/MRC2 Axis

Elevated LINC00909 Promotes Tumor Progression of Ovarian Cancer via Regulating the miR-23b-3p/MRC2 Axis

Role of a Pyroptosis-Related lncRNA Signature in Risk Stratification and Immunotherapy of Ovarian Cancer

The Long Non-Coding RNA SNHG12 as a Mediator of Carboplatin Resistance in Ovarian Cancer via Epigenetic Mechanisms

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