AC138128.1 an Intronic lncRNA originating from ERCC1 Implies a Potential Application in Lung Cancer Treatment

Xiao, Mingyang; Cui, Su; Zhang, Liang; Yu, Tao; Zhang, Guopei; Zhang, Qianye; Li, Liuli; Cai, Yuan; Jin, Cuihong; Yang, Jinghua; Wu, Shengwen; Lu, Xiaobo

doi:10.7150/jca.31832

Cited by 9 publications

(13 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have shown that lncRNA dysregulation is involved in various malignancies, such as lung cancer 4 , esophageal cancer 5 , gastric cancer 6 , liver cancer 7 and PC 8 , 9 , by affecting diverse tumor biological behaviors, such as proliferation, invasion, migration and metastasis, both in vitro and in vivo. Increasing numbers of lncRNA studies in PC have been reported 9 - 12 .…”

Section: Introductionmentioning

confidence: 99%

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Liu¹,

Zheng²,

Zhang³

et al. 2020

Theranostics

View full text Add to dashboard Cite

Background: Due to the limitations of strategies for its early diagnosis and treatment, pancreatic cancer (PC) remains a substantial human health threat. We previously discovered a methylation-mediated lncRNA, LINC00261, which is downregulated in PC tissues. However, the underlying role of LINC00261 in PC remains largely unknown. Methods: Quantitative real-time PCR and in situ hybridization were performed to evaluate the expression levels of LINC00261 in PC, adjacent nontumor and normal pancreas tissues. The clinical significance of LINC00261 was assessed in multicenter PC samples. The functions of LINC00261 in PC were investigated by gain- and loss-of-function assays in vitro and in vivo . Potential downstream pathways and mechanisms were explored via RNA sequencing and bioinformatic analyses. RNA immunoprecipitation and chromatin immunoprecipitation assays were used to validate the underlying mechanisms. Pyrosequencing and targeted demethylation of the LINC00261 promoter were performed to explore the upstream epigenetic mechanisms and therapeutic potential. Results: LINC00261 was significantly downregulated in PC tissues, and its expression was positively associated with the prognosis of PC patients. Phenotypic studies indicated that LINC00261 overexpression significantly suppressed PC cell proliferation, migration and metastasis in vitro and in vivo . c-Myc was identified as a downstream target of LINC00261. LINC00261 repressed c-Myc transcription by physically interacting and binding with the bromo domain of p300/CBP, preventing the recruitment of p300/CBP to the promoter region of c-Myc and decreasing the H3K27Ac level. Moreover, the methylation level of the LINC00261 promoter was high in PC tissues and was correlated with poor prognosis. Targeted demethylation of the LINC00261 promoter inhibited PC progression both in vitro and in vivo . Conclusions: Our findings indicate that methylation-mediated LINC00261 suppresses PC progression by epigenetically repressing c-Myc expression. These findings expand the therapeutic potential of LINC00261, possibly providing evidence to support the development of epigenetic drugs or therapeutic strategies. This research adds further insights into the etiology of PC and indicates that LINC00261 may be a prognostic and therapeutic target in PC.

show abstract

Section: Introductionmentioning

confidence: 99%

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Liu¹,

Zheng²,

Zhang³

et al. 2020

Theranostics

View full text Add to dashboard Cite

show abstract

“…Our previous studies investigated genetic polymorphisms in the 3′‐untranslated region and a long noncoding RNA originating from ERCC1 and their use as biomarkers for prediction of repair of DNA damage and susceptibility to lung cancer. Our results indicate that ERCC1 is significantly regulated at the posttranscriptional level 7,16,17 . Alternative splicing is an important mechanism that regulates gene expression and generates RNA diversity 18 .…”

Section: Introductionmentioning

confidence: 69%

“…Detailed characteristics for all study subjects were provided previously 17 . Study was conducted in accordance to ethical principles stipulated in the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Benzo[a]pyrene diol epoxide‐induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1‐derived circular RNA in pulmonary squamous cell carcinoma

Xiao

Cui

Zhang

et al. 2021

Molecular Carcinogenesis

Self Cite

View full text Add to dashboard Cite

ERCC1 is a gene for repairing DNA damage whose function is related to carcinogenic‐induced tumorigenesis and the effectiveness of platinum therapies. Circular RNAs (circRNAs) are products of posttranscriptional regulation with pleiotropic effects on the pathogenesis of lung cancer. We aim to identify that specific circRNAs derived from ERCC1 can regulate key biological processes involved in the development of lung cancer. We performed bioinformatics analysis, in vitro experiments, and analyzed clinical samples, to determine the biological features of a certain ERCC1‐derived circRNA termed as hsa_circ_0051488 in benzo[a]pyrene diol epoxide‐induced malignant transformed cell and lung cancer cell. The well‐established model of transformed cells provided an ideal platform for analyzing the molecular characteristics of this circRNA in the malignant transformation of lung epithelial cell, which supports that hsa_circ_0051488 functions in the onset and growth of lung squamous cell carcinoma (LUSC). Further analysis indicates that the absence of hsa_circ_0051488 promoted the proliferation of cells with the malignant phenotype. Extensive experiments confirm that hsa_circ_0051488 is present in the cytoplasm and functioned as a competing endogenous RNA. In particular, hsa_circ_0051488 binds to mir‐6717‐5p, thereby modulating the expression of SATB2 gene, a lung cancer suppressor. Furthermore, our in silico experiments indicate that SATB2 can inhibit multiple tumor pathways and its expression positively correlated with the tumor suppressor gene CRMP1. These findings suggest a possible regulatory mechanism of hsa_circ_0051488 in LUSC, and that the newly discovered hsa_circ_0051488/miR‐6717‐5p/SATB2 axis may be a potential route for therapeutic intervention of LUSC.

show abstract

“…Chen et al [ 44 ] showed that the expression level of lnc-RTN2-1 (AC138128.1) in gastric cancer was significantly lower than that in paracancer tissues and associated with the clinicopathological features of gastric cancer. Also, Xiao et al [ 45 ] reported that the lnc-RTN2-1 expression in lung cancer tissue was decreased significantly compared to that in paracancer tissues, and lnc-RTN2-1 increased in a dose- or time-dependent manner after in vitro anticancer drug treatment. These suggested that lnc-RTN2-1 might be of potential value in predicting the diagnosis and treatment of diseases.…”

Section: Discussionmentioning

confidence: 99%

Identification of lncRNA and mRNA Biomarkers in Osteoarthritic Degenerative Meniscus by Weighted Gene Coexpression Network and Competing Endogenous RNA Network Analysis

Zhao

Su²,

Jiao³

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Background. Long noncoding RNAs (lncRNAs) play a crucial role in varieties of biological processes. This study is aimed at investigating meniscal degeneration-specific lncRNAs and mRNAs and their related networks in knee osteoarthritis (KOA). Methods. The dataset GSE98918, which included 24 meniscus samples and related clinical data, was downloaded from the Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNAs in the meniscus between KOA and control groups were identified. Based on the enriched differentially expressed lncRNAs and mRNAs, we constructed the coexpression network using WGCNA (weighted correlation network analysis) and identified the critical module related to KOA. For mRNAs in the key module, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out using the DAVID database. A competing endogenous RNA network (ceRNA) based on the screened mRNAs, lncRNAs, and related miRNAs was constructed to reveal presumptive biomarkers further. Finally, the hub lncRNAs and mRNAs were screened, and the diagnostic value was evaluated using a receiver operating characteristic (ROC) curve. Hub mRNAs were validated using the dataset GSE113825. Results. We screened 208 significantly differentially expressed lncRNAs and mRNAs in menisci between the KOA and non-KOA samples, which were enriched in sixteen modules using WGCNA, especially the green module. Coexpression network based on the enriched differentially expressed lncRNAs and mRNAs in the green module uncovered 5 lncRNAs and 56 mRNAs. The lncRNA-miRNA-mRNA ceRNA network revealed that lnc-HLA-DQA1-5, lnc-RP11-127H5.1.1-1, lnc-RTN2-1, IGFBP4 (insulin-like growth factor binding protein 4), and KLF2 (Kruppel-like factor 2) were significantly correlated with the meniscus degeneration of KOA. ROC curve analysis revealed that these hub lncRNAs and mRNAs showed excellent diagnostic value for KOA. Conclusions. These hub lncRNAs and mRNAs were potential prognostic biomarkers for the meniscus degeneration of KOA. Further studies are required to validate these new biomarkers and better understand the pathological process of the meniscus degeneration of KOA.

show abstract

AC138128.1 an Intronic lncRNA originating from ERCC1 Implies a Potential Application in Lung Cancer Treatment

Cited by 9 publications

References 34 publications

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Benzo[a]pyrene diol epoxide‐induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1‐derived circular RNA in pulmonary squamous cell carcinoma

Identification of lncRNA and mRNA Biomarkers in Osteoarthritic Degenerative Meniscus by Weighted Gene Coexpression Network and Competing Endogenous RNA Network Analysis

Contact Info

Product

Resources

About