Long non-coding RNAs and cancer: a new frontier of translational research?

Spizzo, Riccardo; Almeida, Maria Inês; Colombatti, Alfonso; Calin, George A.

doi:10.1038/onc.2011.621

Cited by 920 publications

(756 citation statements)

References 181 publications

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“…Furthermore, there currently exists no approved targeted therapy for TNBC (lacks estrogen receptor, progesterone receptor and HER2 amplification), which frequently exhibits highly malignant behaviour and resistance to conventional chemotherapies [27]. The identification of novel therapeutic targets for multiple breast cancer subtypes is therefore important, and lncRNAs may offer new opportunities in this regard, given their emerging roles as regulators of fundamental biological processes [1][2][3][4][5]. Indeed, GAS5 is already of particular interest in relation to breast cancer, since its expression is down-regulated in tumour tissue [9], and patient prognosis is significantly related to GAS5 transcript levels [10].…”

Section: Discussionmentioning

confidence: 99%

“…Long ncRNAs (size range: 0.2 -100 kb) are emerging as key regulators of fundamental cellular processes and are increasingly recognized as of importance in the pathogenesis, diagnosis and treatment of major cancers, including breast cancer [1][2][3][4][5]. Apart from ribosomal RNAs, lncRNAs comprise a plethora of mRNA-like transcripts (long intergenic ncRNAs, pseudogene-derived transcripts and sequences that are intronic or antisense to protein coding genes) [1,6,7], which can act as signals, scaffolds, guides, decoys or tethers to modulate, for example, the maintenance of subcellular structures, chromatin modification and transcriptional/post-transcriptional regulation of gene expression [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy

Pickard

Williams

2014

Breast Cancer Res Treat

152

136

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Purpose: The putative tumour suppressor and apoptosis-promoting gene, growth arrestspecific 5 (GAS5), encodes lncRNA and snoRNAs. Its expression is down-regulated in breast cancer, which adversely impacts patient prognosis. In this preclinical study, the consequences of decreased GAS5 expression for breast cancer cell survival following treatment with chemotherapeutic agents are addressed. In addition, functional responses of triple-negative breast cancer cells to GAS5 lncRNA are examined, and mTOR inhibition as a strategy to enhance cellular GAS5 levels is investigated. Methods: Breast cancer cell lines were transfected with either siRNA to GAS5 or with a plasmid encoding GAS5 lncRNA and the effects on breast cancer cell survival were determined. Cellular responses to mTOR inhibitors were evaluated by assaying culture growth and GAS5 transcript levels. Results: GAS5 silencing attenuated cell responses to apoptotic stimuli, including classical chemotherapeutic agents; the extent of cell death was directly proportional to cellular GAS5 levels. Imatinib action in contrast, was independent of GAS5. GAS5 lncRNA promoted the apoptosis of triple-negative and estrogen receptor-positive cells but only dual PI3K/mTOR inhibition was able to enhance GAS5 levels in all cell types. Conclusions: Reduced GAS5 expression attenuates apoptosis induction by classical chemotherapeutic agents in breast cancer cells, providing an explanation for the relationship between GAS5 expression and breast cancer patient prognosis. Clinically, this relationship may be circumvented by the use of GAS5-independent drugs such as imatinib, or by restoration of GAS5 expression. The latter may be achieved by the use of a dual PI3K/mTOR inhibitor, to improve apoptotic responses to conventional chemotherapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy

Pickard

Williams

2014

Breast Cancer Res Treat

152

136

View full text Add to dashboard Cite

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“…These factors include the tremendous complexity and diversity of the lncRNA landscape, the finding that lncRNAs are often located at crucial sites (eg, regions of singlenucleotide polymorphisms (SNPs), amplifications, or at common breakpoints), the presence of sequence motifs and other elements that result in specific structures, their regulation, and their functional relationships with other nucleic acids and proteins. 11,16 In fact, previous studies have shown that particular deregulated lncRNAs are important regulators of tumor formation and progression. 17,24 For example, the antisense intergenic RNA HOX Antisense Intergenic RNA (HOTAIR) is highly expressed in multiple types of primary somatic tumors, such as hepatocellular carcinoma, 25,26 pancreatic cancer, 27 and gastric cancer, 28 as well as some metastatic tumors, including metastatic breast tumors 29 and melanoma.…”

Section: Lncrnas In Cancermentioning

confidence: 99%

“…10 And moreover, a significant proportion of lncRNAs may possess coding and non-coding activities. 11 Combining with these characters, Mercer et al 2 proposed a definition that describes lncRNAs as 'RNA molecules that may function as either primary or spliced transcripts and do not fit into known classes of small RNAs or into classes of structural RNAs'. This undated definition overcomes the restriction of ORF and length that was arbitrarily set.…”

mentioning

confidence: 99%

“…These studies have revealed the functional potential of these molecules; 9,10,13,14 however, the majority of lncRNAs have not yet been functionally characterized.Notably, observations of a few known lncRNAs have suggested that their dysregulation is linked to tumor pathogenesis, and these molecules perform essential regulatory functions by acting on cellular proliferation, apoptosis, or metastasis by participating in a variety of key signaling pathways. 11,[15][16][17] Here, we summarize the recent research concerning alterations in and roles of lncRNAs in cancer pathogenesis, with a specific focus on CRC. Additionally, we discuss the significant and almost wholly untapped potential of lncRNAs as biomarkers for the early diagnosis of CRC, as indicators of CRC prognosis prediction, or even as targets in CRC treatment strategies.…”

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confidence: 99%

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Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Pan

2014

Modern Pathology

102

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Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here we provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential. Keywords: colorectal cancer; diagnosis; dysregulation; long non-coding RNA; prognosis High-throughput genome-scale studies have demonstrated that more than 93% of the DNA sequences in the human genome are actively transcribed. 1 However, only approximately 5-10% of the sequences are stably transcribed into mRNA or non-coding RNA (ncRNA). Genome tiling arrays have revealed that the amount of non-coding sequence is at least four times larger than the amount of coding sequence, which indicates that only 1% of the human genome is composed of protein-coding genes and the remaining 4-9% is transcribed into ncRNAs. 2 Therefore, ncRNAs constitute a very large proportion of the total RNA molecules.The function and clinical significance of short regulatory ncRNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), were elucidated first, 3 and the regulatory roles of miRNAs have been broadly recognized in almost all physiological and pathological processes in the body, including carcinogenesis. 4 For example, we previously reported that MIR95 promotes cell proliferation and targets sorting nexin 1 in human colorectal carcinoma; 5 moreover, in colorectal cancer (CRC) patients, the plasma levels of MIR29a and MIR92a are significantly upregulated and the plasma levels of MIR601 and MIR760 are significantly downregulated; thus the levels of these miRNAs have good diagnostic value for CRC screening. 6,7 According to their transcript size, ncRNAs are grouped into two major classes: (i) small ncRNAs with transcripts o200 nucleotides (nt; eg, aforementioned siRNAs and miRNAs, Piwi-interacting RNAs, and some retrotransposon-derived RNAs) and (ii) long non-coding RNAs (lncRNAs), this class includes five broad categories: sense, antisense, bidirectional, intronic, and intergenic, based on the proximity between neighboring transcripts. 8 For a time, lncRNAs was commonly defined as a proteincoding transcripts that is 4200 nt. 9 However, this definition is arbitrary and ...

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Upregulation of BCAM and its sense lncRNA BAN are associated with gastric cancer metastasis and poor prognosis

et al. 2020

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Patients with metastatic gastric cancer (GC) have a poor prognosis; however, the molecular mechanism of GC metastasis remains unclear. Here, we employed bioinformatics to systematically screen the metastasis‐associated genes and found that the levels of basal cell adhesion molecule (BCAM) were significantly increased in GC tissues from patients with metastasis, as compared to those without metastasis. The upregulation of BCAM was also significantly associated with a shorter survival time. Depletion of BCAM inhibited GC cell migration and invasion. Knockout (KO) of BCAM by the CRISPR/Cas9 system reduced the invasion and metastasis of GC cells. To explore the mechanism of BCAM upregulation, we identified a previously uncharacterized BCAM sense lncRNA that spanned from exon 6 to intron 6 of BCAM, and named it as BCAM‐associated long noncoding RNA (BAN). Knockdown of BAN inhibited BCAM expression at both mRNA and protein levels. Knockdown of BAN suppressed GC cell migration and invasion, which was effectively rescued by ectopic expression of BCAM. Further clinical data showed that BAN upregulation was associated with GC metastasis and poor prognosis. Importantly, BAN expression was also significantly associated with that of BCAM in GC tissues. Taken together, these results indicate that increased expression of BCAM and its sense lncRNA BAN promote GC cell invasion and metastasis, and are associated with poor prognosis of GC patients.

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Long non-coding RNAs and cancer: a new frontier of translational research?

Cited by 920 publications

References 181 publications

Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy

Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Upregulation of BCAM and its sense lncRNA BAN are associated with gastric cancer metastasis and poor prognosis

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