Long non-coding RNAs: a rising biotarget in colorectal cancer

Luo, Jian; Qu, Jian; Wu, Dongkai; Lu, Zuliang; Sun, Yuesheng; Qu, Qiang

doi:10.18632/oncotarget.14728

Cited by 72 publications

(52 citation statements)

References 128 publications

(151 reference statements)

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“…1, and furthermore, GSE18105 [37]: p < 0.0001, logFC = 0.91; GSE9348 [38]: p < 0.0001, logFC = 1.42) also supported its up-regulation in CRC compared to normal controls. However, it must be noted that Zhang YH et al [39] in contrast to the results of other research groups [16][17][18][40][41][42] -published underexpression of LINC00152 in CRC [39]. Our in situ hybridization results in colorectal surgical FFPE tissue sections and TMA slides revealed significant up-regulation of LINC00152 through the normal-adenoma-carcinoma sequence progression, both in epithelial and stromal cells (Fig.…”

Section: Discussioncontrasting

confidence: 61%

Promoter Hypomethylation and Increased Expression of the Long Non-coding RNA LINC00152 Support Colorectal Carcinogenesis

Galamb

Kalmár

Sebestyén

et al. 2020

Pathol. Oncol. Res.

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Up-regulation of the long non-coding RNA LINC00152 can contribute to cancer development, proliferation and invasion, including colorectal cancer, however, its mechanism of action in colorectal carcinogenesis and progression is only insufficiently understood. In this work we correlated LINC00152 expression with promoter DNA methylation changes in colorectal tissues along the normal-adenoma-carcinoma sequence and studied the effects of LINC00152 silencing on the cell cycle regulation and on the whole transcriptome in colon carcinoma cells using cell and molecular biology techniques. LINC00152 was significantly up-regulated in adenoma and colorectal cancer (p < 0.001) compared to normal samples, which was confirmed by real-time PCR and in situ hybridization. LINC00152 promoter hypomethylation detected in colorectal cancer (p < 0.01) was strongly correlated with increased LINC00152 expression (r=-0.90). Silencing of LINC00152 significantly suppressed cell growth, induced apoptosis and decreased cyclin D1 expression (p < 0.05). Whole transcriptome analysis of LINC00152-silenced cells revealed significant down-regulation of oncogenic and metastasis promoting genes (e.g. YES proto-oncogene 1, PORCN porcupine Oacyltransferase), and up-regulation of tumour suppressor genes (e.g. DKK1 dickkopf WNT signalling pathway inhibitor 1, PERP p53 apoptosis effector) (adjusted p < 0.05). Pathway analysis confirmed the LINC00152-related activation of oncogenic molecular pathways including those driven by PI3K/Akt, Ras, WNT, TP53, Notch and ErbB. Our results suggest that promoter hypomethylation related overexpression of LINC00152 can contribute to the pathogenesis of colorectal cancer by facilitating cell progression through the up-regulation of several oncogenic and metastasis promoting pathway elements.

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Section: Discussioncontrasting

confidence: 61%

Promoter Hypomethylation and Increased Expression of the Long Non-coding RNA LINC00152 Support Colorectal Carcinogenesis

Galamb

Kalmár

Sebestyén

et al. 2020

Pathol. Oncol. Res.

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“…Lots of LncRNAs involved in the Wnt pathway are aberrantly expressed in colon cancer, for example CCAT2, CASC11, TINCR, CCAL, cir-ITCH, CTD903, and H19. 43 It is possible that these LncRNAs interrupt or counteract the function of CYTOR and the feed-forward loop. On the other hand, despite the positive feed-forward loop of CYTOR-b-catenin that exerts accelerative effects on metastasis of colon cancer, the master regulator of this loop have not been identified.…”

Section: Discussionmentioning

confidence: 99%

A Positive Feed-Forward Loop between LncRNA-CYTOR and Wnt/β-Catenin Signaling Promotes Metastasis of Colon Cancer

et al. 2018

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We previously demonstrated that long non-coding RNA cytoskeleton regulator RNA (CYTOR), also known as Linc00152, was significantly overexpressed in colon cancer and conferred resistance to oxaliplatin-induced apoptosis. At the same time, elevated CYTOR expression was also reported in gastric cancer and exerted influences on epithelial-mesenchymal transition (EMT) markers. However, the precise mechanism by which CYTOR promotes the EMT phenotype and cancer metastasis remains poorly understood. Here, we showed that loss of epithelial characteristics and simultaneous gain of mesenchymal features correlated with CYTOR expression. Knockdown of CYTOR attenuated colon cancer cell migration and invasion. Conversely, ectopic expression of CYTOR induced an EMT program and enhanced metastatic properties of colon cancer cells. Mechanistically, the binding of CYTOR to cytoplasmic β-catenin impeded casein kinase 1 (CK1)-induced β-catenin phosphorylation that enabled it to accumulate and translocate to the nucleus. Reciprocally, β-catenin/TCF complex enhanced the transcription activity of CYTOR in nucleus, thus forming a positive feed-forward circuit. Moreover, elevated CYTOR, alone or combined with overexpression of nuclear β-catenin, was predictive of poor prognosis. Our findings suggest that CYTOR promotes colon cancer EMT and metastasis by interacting with β-catenin, and the positive feed-forward circuit of CYTOR-β-catenin might be a useful therapeutic target in antimetastatic strategy.

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“…More recent studies have shown that miRNAs can drive the transformation from adenoma to adenocarcinoma [102], and that the micro-RNA 17/92 cluster can regulate the expression of common CRC-associated genes, including BCL3 and PTEN [103,104]. Long ncRNAs, including HOTAIR, CCAT, MALAT-1, H19, and many others, have been associated with CRC development, invasion, and metastasis and with early diagnosis and prognosis [105]. Interestingly, most lncRNAs are also associated with other cancers, suggesting that their functions span several different pathways and cell types.…”

Section: The Gut Microbiome and Non-coding Rnasmentioning

confidence: 99%

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

2019

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In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth. Rates of CRC are increasing in younger individuals, and CRC remains the second most frequent cause of cancer-related deaths globally. Hence, a more in-depth understanding of the role that gut microbes play in CRC is needed. Here, we review recent advances in understanding the impact of gut microbes on the genome and epigenome of CECs, as it relates to CRC. Overall, numerous studies in the past few years have definitively shown that gut microbes exert distinct impacts on DNA damage, DNA methylation, chromatin structure and non-coding RNA expression in CECs. Some of the genes and pathways that are altered by gut microbes relate to CRC development, particularly those involved in cell proliferation and WNT signaling. We need to implement more standardized analysis strategies, collate data from multiple studies, and utilize CRC mouse models to better assess these effects, understand their functional relevance, and leverage this information to improve patient care.

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Long non-coding RNAs: a rising biotarget in colorectal cancer

Cited by 72 publications

References 128 publications

Promoter Hypomethylation and Increased Expression of the Long Non-coding RNA LINC00152 Support Colorectal Carcinogenesis

Promoter Hypomethylation and Increased Expression of the Long Non-coding RNA LINC00152 Support Colorectal Carcinogenesis

A Positive Feed-Forward Loop between LncRNA-CYTOR and Wnt/β-Catenin Signaling Promotes Metastasis of Colon Cancer

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

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