Open Access
ARTICLE
RPSAP52 lncRNA Inhibits p21Waf1/CIP Expression by Interacting With the RNA Binding Protein HuR
Daniela D’Angelo*, Claudio Arra†, Alfredo Fusco*
* Istituto per l’Endocrinologia e l’Oncologia Sperimentale (IEOS) “G. Salvatore,” Consiglio Nazionale delle Ricerche
(CNR) c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM),
Università degli Studi di Napoli “Federico II,” Naples, Italy
† Animal Facility Unit, Istituto Nazionale dei Tumori, Fondazione Pascale, Naples, Italy
Oncology Research 2020, 28(2), 191-201. https://doi.org/10.3727/096504019X15761465603129
Abstract
Long noncoding RNAs have been recently demonstrated to have an important role in fundamental biological processes, and their deregulated expression has been found in several human neoplasias. Our group has
recently reported a drastic overexpression of the long noncoding RNA (lncRNA) RPSAP52 (ribosomal protein SA pseudogene 52) in pituitary adenomas. We have shown that this lncRNA increased cell proliferation
by upregulating the expression of the chromatinic proteins HMGA1 and HMGA2, functioning as a competing endogenous RNA (ceRNA) through competitively binding to microRNA-15a (miR-15a), miR-15b, and
miR-16. The aim of this work was to identify further mechanisms by which RPSAP52 overexpression could
contribute to the development of pituitary adenomas. We investigated the involvement of RPSAP52 in the
modulation of the expression of cell cycle-related genes, such as p21Waf1/CIP, whose deregulation plays a
critical role in pituitary cell transformation. We report that RPSAP52, interacting with the RNA binding protein
HuR (human antigen R), favors the delocalization of miR-15a, miR-15b, and miR-16 on the cyclin-dependent
kinase inhibitor p21Waf1/CIP1 that, accordingly, results in downregulation in pituitary adenomas. A RNA
immunoprecipitation sequencing (RIPseq) analysis performed on cells overexpressing RPSAP52 identified 40
messenger RNAs (mRNAs) enriched in Argonaute 2 (AGO2) immunoprecipitated samples. Among them, we
focused on GAS8 (growth arrest-specific protein 8) gene. Consistently, GAS8 expression was downregulated
in all the analyzed pituitary adenomas with respect to normal pituitary and in RPSAP52-overepressing cells,
supporting the role of RPSAP52 in addressing genes involved in growth inhibition and cell cycle arrest to
miRNA-induced degradation. This study unveils another RPSAP52-mediated molecular mechanism in pituitary tumorigenesis.
Keywords
Cite This Article
APA Style
D’Angelo, D., Arra, C., Fusco, A. (2020). RPSAP52 lncrna inhibits p21waf1/cip expression by interacting with the RNA binding protein hur. Oncology Research, 28(2), 191-201. https://doi.org/10.3727/096504019X15761465603129
Vancouver Style
D’Angelo D, Arra C, Fusco A. RPSAP52 lncrna inhibits p21waf1/cip expression by interacting with the RNA binding protein hur. Oncol Res. 2020;28(2):191-201 https://doi.org/10.3727/096504019X15761465603129
IEEE Style
D. D’Angelo, C. Arra, and A. Fusco "RPSAP52 lncRNA Inhibits p21Waf1/CIP Expression by Interacting With the RNA Binding Protein HuR," Oncol. Res., vol. 28, no. 2, pp. 191-201. 2020. https://doi.org/10.3727/096504019X15761465603129