ePoster Display session ePoster

10P - Emerging role of Telomeric repeat-containing RNA TERRA in hepatocellular carcinoma (ID 257)

Presentation Number
10P
Lecture Time
09:21 - 09:21
Speakers
  • Michele Manganelli (Brescia, Italy)
Session Name
ePoster Display session
Room
ePoster gallery
Date
Tue, 02.03.2021
Time
08:00 - 20:00
Authors
  • Michele Manganelli (Brescia, Italy)
  • Ilaria Grossi (Brescia, Italy)
  • Jessica Corsi (Trento, Italy)
  • Katarina JurikovĂ  (Trento, Italy)
  • Emilio Cusanelli (Trento, Italy)
  • Vito D’agostino (Trento, Italy)
  • Sarah Molfino (Brescia, Italy)
  • Gianluca Baiocchi (Brescia, Italy)
  • Nazario Portolani (Brescia, Italy)
  • Alessandro Salvi (Brescia, Italy)
  • Giuseppina De Petro (Brescia, Italy)

Abstract

Background

Hepatocellular carcinoma (HCC) is the most frequent primary tumor of the liver and the third cause of cancer-related deaths. The identification of candidate molecular targets and biomarkers in HCC clinical practice are needed. The signatures of aberrant long non-coding RNAs (lncRNAs) expression in HCC tissues, their extracellular release and stability had led to their exploration as diagnostic and prognostic tools as well as potential therapeutic targets for HCC. Telomeric-Repeat Containing RNA (TERRA) consists of 100nt-9Kb subtelomeric-derived transcripts able to base-pair with TERC RNA, acting as telomerase allosteric inhibitor. Little is known on the role of lncRNA TERRA in HCC.

Methods

By qPCR we measured TERRA expression in tumor and peritumoral (PT) tissues of HCC patients, as well as in plasma and in HCC cells. HCC patients (n.25) did not receive any treatment before surgical resection. By nickel-based isolation method (NBI) we isolated from the conditioned medium (CM) of HA22T/VGH cells the extracellular vesicles (EVs), subsequently analyzed by qNANO instrument.

Results

Global TERRA expression was significantly downregulated in HCC vs PT tissues (p=0.025) and ROC analysis revealed a significant ability to distinguish HCC from PT (p=0.03). Extracellular TERRA transcripts were significantly higher in plasma of HCC patients compared with healthy subjects and logistic regression model strongly evidenced the potential diagnostic ability of circulating TERRA (AUC=0.76; 95% CI=0.624-0.873; p=0.0004). HA22T/VGH cells expressed TERRA, but most of the transcripts are released into the CM, also encapsulated in EVs (mean diameter=185nm, concentration=163x106/ml). Treatment of HCC cells with the multi-kinase inhibitor (KI) sorafenib significantly increased TERRA expression (p=0.001) and decreased (p=0.01) its release in EVs (mean diameter=252nm, concentration=209x106/ml).

Conclusions

Our results provide evidence on TERRA dysregulation in tissues and liquid biopsy of HCC patients, thus focusing on a novel potential non-invasive biomarker of diagnosis and downstream target of the KI. TERRA detected in the EVs of HCC cells open a new field of cancer research to comprehend its role at the extracellular level.

Legal entity responsible for the study

The authors.

Funding

Lega Italiana Lotta ai Tumori (LILT), Italian Ministry of University and Research (FFRB), University of Brescia.

Disclosure

All authors have declared no conflicts of interest.

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