Human MiR-544a Modulates SELK Expression in Hepatocarcinoma Cell Lines.
Hepatocellular carcinoma (HCC) is a multi-factorial cancer with a very poor prognosis; therefore, there are several investigations aimed at the comprehension of the molecular mechanisms leading to development and progression of HCC and at the definition of new therapeutic strategies. We have recently evaluated the expression of selenoproteins in HCC cell lines in comparison with normal hepatocytes. Recent results have shown that some of them are down- and others up-regulated, including the selenoprotein K (SELK), whose expression was also induced by sodium selenite treatment on cells. However, so far very few studies have been dedicated to a possible effect of microRNAs on the expression of selenoproteins and their implication in HCC. In this study, the analysis of SELK 3'UTR by bioinformatics tools led to the identification of eight sites potentially targeted by human microRNAs. They were then subjected to a validation test based on luciferase reporter constructs transfected in HCC cell lines. In this functional screening, miR-544a was able to interact with SELK 3'UTR suppressing the reporter activity. Transfection of a miR-544a mimic or inhibitor was then shown to decrease or increase, respectively, the translation of the endogenous SELK mRNA. Intriguingly, miR-544a expression was found to be modulated by selenium treatment, suggesting a possible role in SELK induction by selenium.
Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Caserta, Italia.
Nicoletta
N
Potenza
Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Caserta, Italia.
Filomena
F
Castiello
Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Caserta, Italia.
Marta
M
Panella
Servizio di Informatica Medica, Azienda Ospedaliera Universitaria, Seconda Università di Napoli, Napoli, Italia.
Giovanni
G
Colonna
Direttore Scientifico, Istituto Nazionale Tumori "Fondazione G. Pascale"- IRCCS, Napoli, Italia.
Gennaro
G
Ciliberto
Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Caserta, Italia.
Aniello
A
Russo
CROM, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Napoli, Italia.
Susan
S
Costantini
D020413:3' Untranslated Regions; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D012643:Selenium / Q000494:pharmacology; D051140:Selenoproteins / Q000096:biosynthesis* / Q000235:genetics
D020413:3' Untranslated Regions; C582640:MIRN544 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D051140:Selenoproteins; C000592898:selenoprotein K, human; D012643:Selenium