Identification of the lncRNA signature related to Sorafenib effectiveness in liver cancer cells.
Palabras clave:
Cancer, lncRNA, HepatocellularResumen
Hepatocellular carcinoma is the most common form of primary liver cancer being globally recognized as the fourth
cause of cancer-related death [1]. The impact of risk factors on HCC has a variable geographic distribution, including
hepatitis C (HCV) and B (HBV) virus infection, alcohol, aflatoxin B1, metabolic-associated steatotic liver disease
(MASLD), tobacco and congenital diseases. Patients with advanced stage of HCC who lack preserved liver function,
as well as vascular disorders and high blood pressure cannot benefit from the first-line systemic therapies
(Atezolizumab-Bevacizumab and Durvalumab-Tremelimumab), and they are recommended to receive Sorafenib.
Sorafenib is an orally administered multityrosine kinase inhibitor approved by the FDA for the treatment of HCC in
2008 [2, 3]. Among non-coding RNA, miRNAs, lncRNAs and circRNAs have been related to the initiation, progression
and metastasis in HCC [4]. The group has recently shown that miR-512-3p exerts oncogenic role, and miR-200c-3p
exert antitumoral properties under Sorafenib treatment in vitro, in vivo and in two independent cohorts of patients [5].
In this study we focus on lncRNA, a ncRNA molecule of more than 200 nucleotides. LncRNAs carry out many
biological processes, including the regulation of proliferation, invasion, differentiation and metastasis. LncRNA also
regulate gene transcription and translation by modifying the microRNA and mRNA signature in cells [6]. We have
identified the lncRNA signature in response to Sorafenib in two liver cancer cell lines. In silico analysis of RNAseq
data highlighted the differential expression of 11 Sorafenib-regulated lncRNAs in both cell lines. In vitro functional
study validated the results obtained in silico. Sorafenib decreased the expression of 9 lncRNAs and increased the
expression of 1 lncRNA. We will carry out specific experimental approaches to determine the functional role of these
selected lncRNAs in cell invasion and migration. The final outcome of the project would be to determine whether the
lncRNA signature might be a new biomarker of disease prognosis and treatment responsiveness.
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European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. J Hepatol 2018; 69(2): 406-460.
Llovet et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359(4): 378-390. https://doi.org/10.1056/NEJMoa0708857
Cheng et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10(1): 25-34. https://doi.org/10.1016/S1470-2045(08)70285-7
Wong et al. Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications. Nat Rev Gastroenterol Hepatol 2018; 15(3): 137-151. https://doi.org/10.1038/nrgastro.2017.169
de la Cruz-Ojeda et al. miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma. Cells 2022, 11(17), 2673. https://doi.org/10.3390/cells11172673
de la Cruz-Ojeda et al. The Role of Non-Coding RNAs in Autophagy During Carcinogenesis. Frontiers in cell and developmental biology, 10, 799392. https://doi.org/10.3389/fcell.2022.799392
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Derechos de autor 2024 Biosaia: Revista de los másteres de Biotecnología Sanitaria y Biotecnología Ambiental, Industrial y Alimentaria
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-CompartirIgual 4.0.
