LINC00261 Is Differentially Expressed in Pancreatic Cancer Subtypes and Regulates a Pro-Epithelial Cell Identity

Dorn, Ágnes; Glaß, Markus; Neu, Carolin; Heydel, Beate; Hüttelmaier, Stefan; Gutschner, Tony; Haemmerle, Monika

doi:10.3390/cancers12051227

Cited by 21 publications

(20 citation statements)

References 108 publications

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“…LINC00261 is an intergenic non-protein-coding RNA located on chromosome 20p11.21. In PC, LINC00261 has been suggested to be a prognostic marker 18 , but the potential molecular mechanism remains largely unknown 19 , 20 . We validated the expression of LINC00261 from lncRNA microarray data by comparing data from the public cancer databases GEO and TCGA and showed that LINC00261 is downregulated in PC, consistent with the results of previous studies 18 - 20 .…”

Section: Discussionmentioning

confidence: 99%

“…In PC, LINC00261 has been suggested to be a prognostic marker 18 , but the potential molecular mechanism remains largely unknown 19 , 20 . We validated the expression of LINC00261 from lncRNA microarray data by comparing data from the public cancer databases GEO and TCGA and showed that LINC00261 is downregulated in PC, consistent with the results of previous studies 18 - 20 . More importantly, we found by analysis of tissue microarrays established from multicenter cohorts that LINC00261 is an independent protective factor for the survival of PC patients.…”

Section: Discussionmentioning

confidence: 99%

“…Among the numerous dysregulated lncRNAs, the DNA-methylated LINC00261 exhibited markedly lower expression levels in PC tissue than in NP tissue. Previous studies showed that LINC00261 might be a biomarker 18 and metastasis inhibitor in PC 19 , 20 . However, these studies were performed in vitro , possibly limiting the power of their results, and the prognostic value of LINC00261 has not been directly validated in multicenter PC cohorts.…”

Section: Introductionmentioning

confidence: 96%

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

Liu¹,

Zheng²,

Zhang³

et al. 2020

Theranostics

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

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

“…LINC00261 is suggested to act as a tumour-suppressive lincRNA in lung [ 40 ], liver [ 41 ] and gastric cancer [ 42 ]. In pancreatic cancer, LINC00261 was implicated in the epithelial-to-mesenchymal transition (EMT) pathway, which is crucial for metastasis and disease progression [ 27 , 43 ]. Intriguingly, LINC00261 might also be important for human endoderm differentiation [ 44 ] and its reduced expression is a predictor of DFS (see Figure 2 B).…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer

Glaß

Dorn

Hüttelmaier

et al. 2020

Cancers

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Pancreatic ductal adenocarcinomas (PDAC) belong to the deadliest malignancies in the western world. Mutations in TP53 and KRAS genes along with some other frequent polymorphisms occur almost universally and are major drivers of tumour initiation. However, these mutations cannot explain the heterogeneity in therapeutic responses and differences in overall survival observed in PDAC patients. Thus, recent classifications of PDAC tumour samples have leveraged transcriptome-wide gene expression data to account for epigenetic, transcriptional and post-transcriptional mechanisms that may contribute to this deadly disease. Intriguingly, long intervening RNAs (lincRNAs) are a special class of long non-coding RNAs (lncRNAs) that can control gene expression programs on multiple levels thereby contributing to cancer progression. However, their subtype-specific expression and function as well as molecular interactions in PDAC are not fully understood yet. In this study, we systematically investigated the expression of lincRNAs in pancreatic cancer and its molecular subtypes using publicly available data from large-scale studies. We identified 27 deregulated lincRNAs that showed a significant different expression pattern in PDAC subtypes suggesting context-dependent roles. We further analyzed these lincRNAs regarding their common expression patterns. Moreover, we inferred clues on their functions based on correlation analyses and predicted interactions with RNA-binding proteins, microRNAs, and mRNAs. In summary, we identified several PDAC-associated lincRNAs of prognostic relevance and potential context-dependent functions and molecular interactions. Hence, our study provides a valuable resource for future investigations to decipher the role of lincRNAs in pancreatic cancer.

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“…LncRNAs can be subdivided into sense-, antisense-, intronic-, bidirectional-, and long intergenic ncRNAs and are characterized by a minimum length of >200 nt [ 87 , 88 , 89 ]. Importantly, lncRNAs have been shown to play important roles in several human diseases, especially in cancer [ 90 , 91 , 92 , 93 ]. In NSCLC, the expression of lncRNAs was analyzed in platelets in order to identify novel biomarkers of lung cancer.…”

Section: Composition and Sources Of Rna Species In Plateletsmentioning

confidence: 99%

Post-Transcriptional Expression Control in Platelet Biogenesis and Function

Neu

Gutschner

Haemmerle

2020

IJMS

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Platelets are highly abundant cell fragments of the peripheral blood that originate from megakaryocytes. Beside their well-known role in wound healing and hemostasis, they are emerging mediators of the immune response and implicated in a variety of pathophysiological conditions including cancer. Despite their anucleate nature, they harbor a diverse set of RNAs, which are subject to an active sorting mechanism from megakaryocytes into proplatelets and affect platelet biogenesis and function. However, sorting mechanisms are poorly understood, but RNA-binding proteins (RBPs) have been suggested to play a crucial role. Moreover, RBPs may regulate RNA translation and decay following platelet activation. In concert with other regulators, including microRNAs, long non-coding and circular RNAs, RBPs control multiple steps of the platelet life cycle. In this review, we will highlight the different RNA species within platelets and their impact on megakaryopoiesis, platelet biogenesis and platelet function. Additionally, we will focus on the currently known concepts of post-transcriptional control mechanisms important for RNA fate within platelets with a special emphasis on RBPs.

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LINC00261 Is Differentially Expressed in Pancreatic Cancer Subtypes and Regulates a Pro-Epithelial Cell Identity

Cited by 21 publications

References 108 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

Comprehensive Analysis of LincRNAs in Classical and Basal-Like Subtypes of Pancreatic Cancer

Post-Transcriptional Expression Control in Platelet Biogenesis and Function

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