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Title: Gene Amplification-Associated Overexpression of the Selenoprotein tRNA Enzyme TRIT1 Confers Sensitivity to Arsenic Trioxide in Small-Cell Lung Cancer
Author: Coll Sanmartin, Laia
Davalos, Veronica
Piñeyro, David
Rosselló Tortella, Margalida
Bueno Costa, Alberto
Setién, Fernando
Villanueva Garatachea, Alberto
Granada, Isabel
Ruiz Xiviller, Neus
Kotter, Annika
Helm, Mark
Yokota, Jun
Kawabata Iwakawa, Reika
Kohno, Takashi
Esteller, Manel
Keywords: Càncer de pulmó
Lung cancer
Issue Date: 14-Apr-2021
Publisher: MDPI
Abstract: The alteration of RNA modification patterns is emerging as a common feature of human malignancies. If these changes affect key RNA molecules for mRNA translation, such as transfer RNA, they can have important consequences for cell transformation. TRIT1 is the enzyme responsible for the hypermodification of adenosine 37 in the anticodon region of human tRNAs containing serine and selenocysteine. Herein, we show that TRIT1 undergoes gene amplification-associated overexpression in cancer cell lines and primary samples of small-cell lung cancer. From growth and functional standpoints, the induced depletion of TRIT1 expression in amplified cells reduces their tumorigenic potential and downregulates the selenoprotein transcripts. We observed that TRIT1-amplified cells are sensitive to arsenic trioxide, a compound that regulates selenoproteins, whereas reduction of TRIT1 levels confers loss of sensitivity to the drug. Overall, our results indicate a role for TRIT1 as a small-cell lung cancer-relevant gene that, when undergoing gene amplification-associated activation, can be targeted with the differentiation agent arsenic trioxide.
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It is part of: Cancers, 2021, vol. 13, num. 8
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Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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