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Article

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

1
Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, 25123 Brescia, Italy
2
Department of Cellular, Computational and Integrative Biology, CIBIO, University of Trento, 38123 Trento, Italy
3
Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, 25123 Brescia, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Daniela Gabbia and Sara De Martin
Int. J. Mol. Sci. 2022, 23(11), 6183; https://doi.org/10.3390/ijms23116183
Received: 27 April 2022 / Revised: 26 May 2022 / Accepted: 29 May 2022 / Published: 31 May 2022
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. View Full-Text
Keywords: hepatocellular carcinoma; telomeric-repeat-containing RNAs (TERRA); TERC; TERT mRNA; extracellular vesicles hepatocellular carcinoma; telomeric-repeat-containing RNAs (TERRA); TERC; TERT mRNA; extracellular vesicles
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MDPI and ACS Style

Manganelli, M.; Grossi, I.; Corsi, J.; D’Agostino, V.G.; Jurikova, K.; Cusanelli, E.; Molfino, S.; Portolani, N.; Salvi, A.; De Petro, G. Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma. Int. J. Mol. Sci. 2022, 23, 6183. https://doi.org/10.3390/ijms23116183

AMA Style

Manganelli M, Grossi I, Corsi J, D’Agostino VG, Jurikova K, Cusanelli E, Molfino S, Portolani N, Salvi A, De Petro G. Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2022; 23(11):6183. https://doi.org/10.3390/ijms23116183

Chicago/Turabian Style

Manganelli, Michele, Ilaria Grossi, Jessica Corsi, Vito Giuseppe D’Agostino, Katarina Jurikova, Emilio Cusanelli, Sarah Molfino, Nazario Portolani, Alessandro Salvi, and Giuseppina De Petro. 2022. "Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma" International Journal of Molecular Sciences 23, no. 11: 6183. https://doi.org/10.3390/ijms23116183

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