Downregulation of lncRNA APCDD1L-AS1 due to DNA hypermethylation and loss of VHL protein expression promotes the progression of clear cell renal cell carcinoma

Yang, Wuping; Zhou, Jingcheng; Zhang, Zedan; Zhang, Kenan; Xu, Yawei; Li, Lei; Cai, Lin; Gong, Yanqing; Gong, Kan

doi:10.7150/ijbs.71519

Cited by 9 publications

(5 citation statements)

References 48 publications

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“…Previous studies have revealed that the abnormal expression of APCDD1L‐AS1 was related to the tumor growth and metastasis, prognosis, and drug resistance in clear cell renal cell carcinoma, lung adenocarcinoma and squamous cell carcinoma, and oral squamous cell carcinoma. 34 , 35 , 36 , 37 MIR210HG is located at 11p15.5 which is associated with tumor cell proliferation and metastasis in endometrial cancer, breast cancer, cervical cancer, NSCLC, and gastric cancer. 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 RP11‐21 L19.1 located in 11p15.2, and the low expression of which was significantly related with a poor prognosis in kidney renal papillary cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…APCDD1L‐AS1 located in 20q13.32. Previous studies have revealed that the abnormal expression of APCDD1L‐AS1 was related to the tumor growth and metastasis, prognosis, and drug resistance in clear cell renal cell carcinoma, lung adenocarcinoma and squamous cell carcinoma, and oral squamous cell carcinoma 34–37 . MIR210HG is located at 11p15.5 which is associated with tumor cell proliferation and metastasis in endometrial cancer, breast cancer, cervical cancer, NSCLC, and gastric cancer 38–45 .…”

Section: Discussionmentioning

confidence: 99%

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Cervical cancer‐specific long non‐coding RNA landscape reveals the favorable prognosis predictive performance of an ion‐channel‐related signature model

Wang,

Zhou

et al. 2024

Cancer Medicine

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BackgroundIon channels play an important role in tumorigenesis and progression of cervical cancer. Multiple long non‐coding RNA genes are widely involved in ion channel‐related signaling regulation. However, the association and potential clinical application of lncRNAs in the prognosis of cervical cancer are still poorly explored.MethodsThirteen patients with cervical cancer were enrolled in current study. Whole transcriptome (involving both mRNAs and lncRNAs) sequencing was performed on fresh tumor and adjacent normal tissues that were surgically resected from patients. A comprehensive cervical cancer‐specific lncRNA landscape was obtained by our custom pipeline. Then, a prognostic scoring model of ion‐channel‐related lncRNAs was established by regression algorithms. The performance of the predictive model as well as its association with the clinical characteristics and tumor microenvironment (TME) status were further evaluated.ResultsTo comprehensively identify cervical cancer‐specific lncRNAs, we sequenced 26 samples of cervical cancer patients and integrated the transcriptomic results. We built a custom analysis pipeline to improve the accuracy of lncRNA identification and functional annotation and obtained 18,482 novel lncRNAs in cervical cancer. Then, 159 ion channel‐ and tumorigenesis‐related (ICTR‐) lncRNAs were identified. Based on nine ICTR‐lncRNAs, we also established a prognostic scoring model and validated its accuracy and robustness in assessing the prognosis of patients with cervical cancer. Besides, the TME was characterized, and we found that B cells, activated CD8+ T, and tertiary lymphoid structures were significantly associated with ICTR‐lncRNAs signature scores.ConclusionWe provided a thorough landscape of cervical cancer‐specific lncRNAs. Through integrative analyses, we identified ion‐channel‐related lncRNAs and established a predictive model for assessing the prognosis of patients with cervical cancer. Meanwhile, we characterized its association with TME status. This study improved our knowledge of the prominent roles of lncRNAs in regulating ion channel in cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cervical cancer‐specific long non‐coding RNA landscape reveals the favorable prognosis predictive performance of an ion‐channel‐related signature model

Wang,

Zhou

et al. 2024

Cancer Medicine

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“…Within ccRCC, specific genes undergoing DNA hypermethylation contribute to the promotion of cancer growth and metastasis. Notably, this includes the downregulation of lncRNA ZNF582-AS1 and lncRNA APCDD1L-AS1, both of which exert regulatory control over the progression of ccRCC [40,41]. In colorectal cancer, elevated methylation of TMEM25 exhibits an inverse correlation with its expression [18].…”

Section: Discussionmentioning

confidence: 99%

Multidimensional comprehensive and integrated analysis of the potential function of TMEM25 in renal clear cell carcinoma with low expression status

Xi,

Zhang,

Liu

et al. 2024

Aging

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Background: Transmembrane 25(TMEM25) stands out as a potential prognostic biomarker and therapeutic target in the realm of cancer, yet its precise mechanism of action within clear cell renal cell carcinoma (ccRCC) remains unclear. Materials and Methods: Gene expression data and clinically relevant information extracted from The Cancer Genome Atlas (TCGA) and Gene expression omnibus (GEO) databases unveil the expression patterns of TMEM25 within renal clear cell carcinoma, which reveals its prognostic and diagnostic significance. The protein expression data is available via the Human Protein Atlas (HPA) database. Further, qPCR experiments conducted on cells and tissues provide strong evidence of the gene's expression status. Additionally, they explore the correlations between TMEM25 expression and DNA methylation, gene mutations, immune cell infiltration, and drug sensitivity within this specific tumor context. Results: At both the RNA and protein levels, TMEM25 displays a noteworthy downregulation in expression, which is consistently linked to an unfavorable prognosis. Receiver Operating Characteristic (ROC) curve analysis, univariate and multivariate Cox regression analyses confirmed the ability of TMEM25 to diagnose and determine prognosis in ccRCC. Its expression related closely with various immune cell types, immune checkpoints, immune inhibitors, and MHC molecules. Within ccRCC tissues, TMEM25 DNA methylation levels are observed to be elevated, and this upregulation is observed across various conditions. TMEM25 mutations also have an impact on the prognosis of ccRCC patients and the results of drug sensitivity analyses are useful for clinical decision-making. Conclusions: TMEM25 in ccRCC could potentially function as a tumor suppressor gene, holding substantial promise as a novel biomarker for diagnosing, treating, and prognosticating ccRCC patients.

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“…Overexpressing APCDD1L-AS1, a novel lncRNA, inhibited the growth and metastasis of ccRCC cells in vitro and in vivo . Dysregulation of histone expression caused by APCDD1L-AS1 overexpression may also inhibit ccRCC progression ( 40 ). However, APCDD1L-AS1 expression was decreased by DNA hypermethylation and inactivation of von Hippel Lindau (VHL) protein expression.…”

Section: Discussionmentioning

confidence: 99%

Novel methylation-related long non-coding RNA clinical outcome prediction method: the clinical phenotype and immune infiltration research in low-grade gliomas

Li¹,

Li²,

Yu³

2023

Front. Oncol.

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BackgroundRecent studies have suggested that long non-coding RNAs (lncRNAs) may play crucial role in low-grade glioma; however, the underlying mechanisms linking them to epigenetic methylation remain unclear.MethodsWe downloaded expression level data for regulators associated with N1 methyladenosine (m1A), 5-methyladenine (m5C), and N6 methyladenosine (m6A) (M1A/M5C/M6A) methylation from the Cancer Genome Atlas-low-grade glioma (TCGA-LGG) database. We identified the expression patterns of lncRNAs, and selected methylation-related lncRNAs using Pearson correlation coefficient>0.4. Non-negative matrix dimensionality reduction was then used to determine the expression patterns of the methylation-associated lncRNAs. We constructed a weighted gene co-expression network analysis (WGCNA) network to explore the co-expression networks between the two expression patterns. Functional enrichment of the co-expression network was performed to identify biological differences between the expression patterns of different lncRNAs. We also constructed prognostic networks based on the methylation presence in lncRNAs in low-grade gliomas.ResultsWe identified 44 regulators by literature review. Using a correlation coefficient greater than 0.4, we identified 2330 lncRNAs, among which 108 lncRNAs with independent prognostic values were further screened using univariate Cox regression at P< 0.05. Functional enrichment of the co-expression networks revealed that regulation of trans-synaptic signaling, modulation of chemical synaptic transmission, calmodulin binding, and SNARE binding were mostly enriched in the blue module. The calcium and CA2 signaling pathways were associated with different methylation-related long non-coding chains. Using the Least Absolute Shrinkage Selector Operator (LASSO) regression analysis, we analyzed a prognostic model containing four lncRNAs. The model’s risk score was 1.12 *AC012063 + 0.74 * AC022382 + 0.32 * AL049712 + 0.16 * GSEC. Gene set variation analysis (GSVA) revealed significant differences in mismatch repair, cell cycle, WNT signaling pathway, NOTCH signaling pathway, Complement and Cascades, and cancer pathways at different GSEC expression levels. Thus, these results suggest that GSEC may be involved in the proliferation and invasion of low-grade glioma, making it a prognostic risk factor for low-grade glioma.ConclusionOur analysis identified methylation-related lncRNAs in low-grade gliomas, providing a foundation for further research on lncRNA methylation. We found that GSEC could serve as a candidate methylation marker and a prognostic risk factor for overall survival in low-grade glioma patients. These findings shed light on the underlying mechanisms of low-grade glioma development and may facilitate the development of new treatment strategies.

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Downregulation of lncRNA APCDD1L-AS1 due to DNA hypermethylation and loss of VHL protein expression promotes the progression of clear cell renal cell carcinoma

Cited by 9 publications

References 48 publications

Cervical cancer‐specific long non‐coding RNA landscape reveals the favorable prognosis predictive performance of an ion‐channel‐related signature model

Cervical cancer‐specific long non‐coding RNA landscape reveals the favorable prognosis predictive performance of an ion‐channel‐related signature model

Multidimensional comprehensive and integrated analysis of the potential function of TMEM25 in renal clear cell carcinoma with low expression status

Novel methylation-related long non-coding RNA clinical outcome prediction method: the clinical phenotype and immune infiltration research in low-grade gliomas

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