LncRNAs as novel players in hepatocellular carcinoma recurrence
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Laura Gramantieri1,*, Michele Baglioni1,*, Francesca Fornari1,2, Maria Antonella Laginestra3, Manuela Ferracin3, Valentina Indio4, Matteo Ravaioli5, Matteo Cescon2,5, Vanessa De Pace5, Simona Leoni1, Camelia Alexandra Coadă1, Massimo Negrini6, Luigi Bolondi1,2 and Catia Giovannini1,2
1Center for Applied Biomedical Research, St. Orsola-Malpighi University Hospital, Bologna, Italy
2Department of Medical and Surgical Sciences, DIMEC, University of Bologna, Bologna, Italy
3Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
4“Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, Italy
5General Surgery and Transplant Unit, Sant’Orsola-Malpighi University Hospital, Bologna, Italy
6Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
*These authors have contributed equally to this work
Laura Gramantieri, email: [email protected]
Catia Giovannini, email: [email protected]
Keywords: hepatocellular carcinoma; LUCAT1; CASC9; biomarkers
Received: March 07, 2018 Accepted: September 01, 2018 Published: October 12, 2018
Long non-coding RNAs (lncRNAs) are ncRNAs more than 200 nucleotides long that participate to a wide range of biological functions. However, their role in cancer is poorly known. By using an NGS-based approach we analyzed the intragenic and poliA-lncRNAs in hepatocellular carcinoma (HCC) and we assayed the relationships between their deregulated expression and clinical-pathological characteristics. The expression profile of lncRNAs was studied in a discovery series of 28 HCC and matched cirrhosis and was validated in an independent cohort of 32 HCC patients both in tissue and serum. The correlation between lncRNA expression and clinical-pathological variables, EMT markers and putative sponged microRNAs level were investigated. Functional experiments were performed in HCC-derived cell lines to clarify the role of selected lncRNAs in HCC. A panel of deregulated lncRNAs differentiated HCC from cirrhotic tissue. CASC9 and LUCAT1 were up-regulated in a subset of HCC-derived cell lines and in half of HCCs which displayed a lower recurrence after surgery. LUCAT1 and CASC9 silencing increased cell motility and invasion capability in HCC cells and influenced the EMT phenotype. LUCAT1 was demonstrated to directly sponge the onco-miR-181d-5p. Both LUCAT1 and CASC9 were secreted in exosomes, and higher circulating CASC9 levels were associated with tumor size and HCC recurrence after surgery, suggesting its potential usage as putative non-invasive prognostic biomarker of recurrence.
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