Long non-coding RNAs at work on telomeres: Functions and implications in cancer therapy

Gala, Kavita; Khattar, Ekta

doi:10.1016/j.canlet.2020.12.036

Cited by 26 publications

(21 citation statements)

References 149 publications

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“…Considering the evidence provided by the present study on the altered expression of TERRA , TERC and TERT mRNA in HCC tissues and on the detection of TERRA and TERC in the plasma of HCC patients, we aimed to explore the cellular and extracellular expression of these transcripts in human HCC cell lines in order to gain mechanistic insights on the function of TERRA in HCC. Since TERRA transcripts may participate in the cellular response to anticancer compounds [ 10 , 11 , 12 ], first we assessed the transcript expression in HA22T/VGH and SKHep1C3 cells ( Figure 6 ) and monitored the possible expression variation following an anticancer drug treatment, in particular the sorafenib treatment in sensitive and resistant cells (sf and SR cells, respectively) [ 22 , 23 ]; this is because sorafenib is one of the drugs used by clinicians for the treatment of advanced HCC [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

“…Expression studies conducted by various technologies have revealed the dysregulation of TERRA in various solid tumors, a frequent downregulation in specific tumor types vs. their normal tissue counterparts [ 8 ], but also its overexpression in medulloblastoma [ 9 ]. Moreover TERRA expression is increased upon the treatment of human cancer cell lines with chemotherapeutic agents, suggesting that TERRA transcripts may participate in the cellular response and/or resistance to chemotherapy [ 10 , 11 , 12 ]. For hepatocellular carcinoma (HCC), it is known that telomerase activation is a hallmark of this malignant condition [ 13 ] and that TERRA may participate in telomerase regulation in this cancer type [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma

Manganelli

Grossi

Corsi

et al. 2022

IJMS

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Non-coding RNAs are transcribed from telomeres and the telomeric repeat-containing RNAs (TERRA) are implicated in telomere homeostasis and in cancer. In this study, we aimed to assess in hepatocellular carcinoma (HCC) the cellular and extracellular expression of TERRA, the telomerase RNA subunit (TERC) and the telomerase catalytic subunit (TERT). We determined by qPCR the expression level of TERRA 1_2_10_13q, TERRA 15q, TERRA XpYp, TERC and of TERT mRNA in HCC tissues and in the plasma of HCC patients. Further, we profiled the same transcripts in the HCC cell lines, HA22T/VGH and SKHep1C3, and in the extracellular vesicles (EVs) derived from their secretomes. We found that the expression of TERRA and TERT mRNA was significantly deregulated in HCC, being TERRA downregulated and TERT mRNA upregulated in HCC tissues vs. the peritumoral (PT) ones, and the receiver operating characteristic (ROC) curve analyses revealed a significant ability in discriminating HCC from PT tissue. Further, the determinations of circulating TERRA and TERC showed higher amounts of these transcripts in the plasma of HCC patients vs. controls and ROC analyses gave significant results. The expression characterization of the cultured HCC cells showed their ability to produce and secrete TERRA and TERC into the EVs; the ability to produce TERT mRNA that was not detectable in the EVs; and the ability to respond to sorafenib treatment increasing TERRA expression. Our results highlight that: (i) both cellular and extracellular expressions of TERRA and TERC are dysregulated in HCC as well as the cellular expression of TERT mRNA and (ii) the combined detection of TERRA and TERC in plasma may represent a promising approach for non-invasive diagnostic molecular indicators of HCC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma

Manganelli

Grossi

Corsi

et al. 2022

IJMS

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“…Finally, RNA G4 have been found also in lncRNAs [ 23 ]. For instance, the G-rich element at the 5′ end of TERC —the RNA moiety of telomerase that contains the template sequence for the de novo synthesis of telomeric repeats—may fold into a G4.…”

Section: Introductionmentioning

confidence: 99%

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Alessandrini

Recagni

Zaffaroni

et al. 2021

IJMS

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Nucleic acid sequences able to adopt a G-quadruplex conformation are overrepresented within the human genome. This evidence strongly suggests that these genomic regions have been evolutionary selected to play a pivotal role in several aspects of cell biology. In the present review article, we provide an overview on the biological impact of targeting G-quadruplexes in cancer. A variety of small molecules showing good G-quadruplex stabilizing properties has been reported to exert an antitumor activity in several preclinical models of human cancers. Moreover, promiscuous binders and multiple targeting G-quadruplex ligands, cancer cell defense responses and synthetic lethal interactions of G-quadruplex targeting have been also highlighted. Overall, evidence gathered thus far indicates that targeting G-quadruplex may represent an innovative and fascinating therapeutic approach for cancer. The continued methodological improvements, the development of specific tools and a careful consideration of the experimental settings in living systems will be useful to deepen our knowledge of G-quadruplex biology in cancer, to better define their role as therapeutic targets and to help design and develop novel and reliable G-quadruplex-based anticancer strategies.

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“…Further proof of the methodology was achieved by quantifying a second telomere-related lncRNA, TERC, one of the two main subunits of telomerase, highly related to telomeres and TERRA dynamics and of great importance in malignisation and inflammatory responses 16 as well as in the prognosis of human cancer and other diseases 6 , 17 . Currently, the analysis of TERC expression is conducted using RT-qPCR 17 , 18 .…”

Section: Resultsmentioning

confidence: 99%

“…LncRNAs have been postulated as biomarkers for the diagnosis and prognosis of various diseases such as cancer 1 and they have been indicated as new therapeutic targets 2 , 3 . Two of those candidates are the telomeric associated lncRNAs TERRA and TERC, whose levels are altered in cancer cells 4 and other diseases 5 and have been lately postulated as therapeutic targets in cancer 3 , 6 .…”

Section: Introductionmentioning

confidence: 99%

Quantifying telomeric lncRNAs using PNA-labelled RNA-Flow FISH (RNA-Flow)

Gonzalez-Vasconcellos

Cobos-Fernández

Atkinson

et al. 2022

Commun Biol

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Here we present a method to detect and quantify long non-coding RNAs, in particular those related to telomeres. By coupling the specificity of a peptide nucleic acid (PNA) probe with flow cytometry we have quantified cellular levels of TERRA and TERC lncRNAs in culture cell lines and PBMCs. This easy-to-use method appointed RNA-Flow allows reliable lncRNA quantification with broad applications in basic research and clinical diagnostics. In addition, the staining protocol presented here was proven useful for the detection and quantification of such lncRNAs on unfixed cells using confocal microscopy.

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Long non-coding RNAs at work on telomeres: Functions and implications in cancer therapy

Cited by 26 publications

References 149 publications

Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma

Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Quantifying telomeric lncRNAs using PNA-labelled RNA-Flow FISH (RNA-Flow)

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