Next Article in Journal
Deciphering the Elevated Lipid via CD36 in Mantle Cell Lymphoma with Bortezomib Resistance Using Synchrotron-Based Fourier Transform Infrared Spectroscopy of Single Cells
Previous Article in Journal
Integrative In Vivo Drug Testing Using Gene Expression Signature and Patient-Derived Xenografts from Treatment-Refractory HER2 Positive and Triple-Negative Subtypes of Breast Cancer
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle

HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia

Ageing Research Center and Translational medicine-CeSI-MeT, 66100 Chieti, Italy
Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University Chieti-Pescara, 66100 Chieti, Italy
Department of Medicine and Aging Sciences, “G. d’Annunzio” University Chieti-Pescara, 66100 Chieti, Italy
Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
Institute of Hematology, Catholic University of the Sacred Heart, 00168 Rome, Italy
Department of Medicine, Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
Chronic Lymphocytic Leukemia Research Consortium, San Diego, CA 92093, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(4), 575;
Received: 20 March 2019 / Revised: 15 April 2019 / Accepted: 19 April 2019 / Published: 23 April 2019
PDF [8643 KB, uploaded 23 April 2019]
  |     |  


Aneuploidy and overexpression of hsa-miR-155-5p (miR-155) characterize most solid and hematological malignancies. We recently demonstrated that miR-155 sustains aneuploidy at early stages of in vitro cellular transformation. During in vitro transformation of normal human fibroblast, upregulation of miR-155 downregulates spindle checkpoint proteins as the mitotic checkpoint serine/threonine kinase budding uninhibited by benzimidazoles 1 (BUB1), the centromere protein F (CENPF) and the zw10 kinetochore protein (ZW10), compromising the chromosome alignment at the metaphase plate and leading to aneuploidy in daughter cells. Here we show that the heterogeneous nuclear ribonucleoprotein L (HNRNPL) binds to the polymorphic marker D2S1888 at the 3′UTR of BUB1 gene, impairs the miR-155 targeting, and restores BUB1 expression in chronic lymphocytic leukemia. This mechanism occurs at advanced passages of cell transformation and allows the expansion of more favorable clones. Our findings have revealed, at least in part, the molecular mechanisms behind the chromosomal stabilization of cell lines and the concept that, to survive, tumor cells cannot continuously change their genetic heritage but need to stabilize the most suitable karyotype. View Full-Text
Keywords: miR-155; BUB1; HNRNPL; CIN; CLL and microRNA miR-155; BUB1; HNRNPL; CIN; CLL and microRNA

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Pagotto, S.; Veronese, A.; Soranno, A.; Balatti, V.; Ramassone, A.; Guanciali-Franchi, P.E.; Palka, G.; Innocenti, I.; Autore, F.; Rassenti, L.Z.; Kipps, T.J.; Mariani-Costantini, R.; Laurenti, L.; Croce, C.M.; Visone, R. HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia. Cancers 2019, 11, 575.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top