Exploring the mechanisms behind long noncoding RNAs and cancer

Balas, Maggie M.; Johnson, Aaron

doi:10.1016/j.ncrna.2018.03.001

Cited by 229 publications

(183 citation statements)

References 116 publications

(199 reference statements)

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“…Additionally, we showed that our gene lists contain many non-coding RNA genes, primarily consisting of lncRNAs, suggesting that methylation alterations at non-coding gene promoters are frequently present in cancer. This fits with the growing body of research showing that lncRNAs and other non-coding RNAs play a key role in cancer [30,31,32].…”

Section: Discussionsupporting

confidence: 83%

Machine Classification of Methylomes in Cancer

Newsham

Sendera

Jammula

et al. 2020

Preprint

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Cancer remains a leading cause of morbidity and mortality worldwide. Its evolutionary nature and resultant complex interactions with the tumour micro-environment and the host immune system engender heterogeneity, make developing interventions difficult. Usually detected at the advanced stages of disease, metastatic cancer accounts for 90% of cancer-associated deaths. Therefore early detection of cancer, combined with current therapies, would have a significant impact on survival and treatment of this insidious disease. Epigenetic changes such as DNA methylation are some of the early events in carcinogenesis. Here, we report on a machine learning model that can classify 13 types of cancer as well as non-cancer tissue samples using only DNA methylome data, with an accuracy of 98.2%. We utilise the features identified by this model to develop a robust deep neural network that can generalise to independent data sets. We also demonstrate that the methylation associated genomic loci detected by the classifier are associated with genes involved in cancer, providing insights into the epigenomic regulation of carcinogenesis.

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Section: Discussionsupporting

confidence: 83%

Machine Classification of Methylomes in Cancer

Newsham

Sendera

Jammula

et al. 2020

Preprint

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“…It has been suggested that lncRNAs can interact with transcriptional regulators/co-factors to form ribonucleoprotein (RNP) complexes to regulate the expression of downstream genes in the cell nucleus (40). To identify MaTAR25 interacting proteins we used two different paired sets of biotin-labeled antisense oligonucleotides targeting MaTAR25 for native RNA antisense oligonucleotide pull-down (RAP) in 4T1 cells followed by qRT-PCR which revealed a 50-60% pull-down efficiency (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

MaTAR25LncRNA Regulates theTensin1Gene to Impact Breast Cancer Progression

Chang

Diermeier

et al. 2020

Preprint

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SUMMARYMisregulation of long non-coding RNA genes has been linked to a wide variety of cancer types. Here we report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo. MaTAR25 functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene Tensin 1 (Tns1) to regulate its expression in trans. Knockout of MaTAR25 results in down-regulation of Tns1 leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. The human ortholog of MaTAR25, LINC01271, is upregulated with human breast cancer stage and metastasis. SIGNIFICANCE LncRNAs have great potential to reveal new regulatory mechanisms of function as well as having exciting therapeutic capacity given their ease of being targeted by nucleic acid drugs. Our study of MaTAR25, and its human ortholog LINC01271, reveal an unexpected function of this lncRNA in breast cancer progression by regulating Tns1 gene expression, whose protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. We identified LINC01271 as the human ortholog of MaTAR25, and importantly, increased expression of LINC01271 is associated with poor patient prognosis and cancer metastasis. Our findings demonstrate that LINC01271 represents an exciting therapeutic target to alter breast cancer progression.

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“…High expression of HOTAIR has been implicated in various types of malignancies, and it plays a critical role in most biologic processes of cancer. 14…”

Section: Introductionmentioning

confidence: 99%

Delphinidin suppresses breast carcinogenesis through the HOTAIR/microRNA‐34a axis

et al. 2019

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Delphinidin, one of the main anthocyanidins, has potent anti‐cancer properties. In this study, we investigated the effect of delphinidin on 1‐methyl‐1‐nitrosourea (MNU)‐induced breast carcinogenesis on rats and the mechanism of delphinidin via negative regulation of the HOTAIR/microRNA‐34a axis. We found administration of delphinidin could effectively suppress MNU‐induced mammal breast carcinogenesis. Delphinidin downregulated the level of HOTAIR and upregulated miR‐34a in breast carcinogenesis. Western blot analysis confirmed that delphinidin treatment can significantly decrease the expression of β‐catenin, glycogen synthase kinase‐3β (Gsk3β), c‐Myc, cyclin‐D1, and matrix metalloproteinase‐7(MMP‐7) expression in breast cancer cells, and inhibition of miR‐34a significantly reduced the effect of delphinidin on c‐Myc, cyclin‐D1, and MMP‐7. HOTAIR overexpression also blocked the effect of delphinidin on miR‐34a and the Wnt/β‐catenin signaling pathway in MDA‐MB‐231 cells. RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay results showed that delphinidin upregulated miR‐34a by inhibiting HOTAIR, coupled with enhancement of the zeste homolog 2 (EZH2) and histone H3 Lys27 trimethylation (H3K27me3). This study indicated that delphinidin may potentially suppress breast carcinogenesis and exert its anti‐cancer effect through the HOTAIR/miR‐34a axis. These findings provided new evidence for the use of delphinidin in preventing breast carcinogenesis.

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Exploring the mechanisms behind long noncoding RNAs and cancer

Cited by 229 publications

References 116 publications

Machine Classification of Methylomes in Cancer

Machine Classification of Methylomes in Cancer

MaTAR25LncRNA Regulates theTensin1Gene to Impact Breast Cancer Progression

Delphinidin suppresses breast carcinogenesis through the HOTAIR/microRNA‐34a axis

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