Predictive Potential of RNA Polymerase B (II) Subunit 1 (RPB1) Cytoplasmic Aggregation for Neoadjuvant Chemotherapy Failure

Bence Nagy-Mikó; Orsolya Németh-Szatmári; Réka Faragó-Mészáros; Aliz Csókási; Bence Bognár; Nóra Ördög; Barbara N Borsos; Hajnalka Majoros; Zsuzsanna Ujfaludi; Orsolya Oláh-Németh; Aliz Nikolényi; Ágnes Dobi; Renáta Kószó; Dóra Sántha; György Lázár; Zsolt Simonka; Attila Paszt; Katalin Ormándi; Tibor Pankotai; Imre M Boros; Zoltán Villányi; András Vörös

doi:10.3390/ijms242115869

Predictive Potential of RNA Polymerase B (II) Subunit 1 (RPB1) Cytoplasmic Aggregation for Neoadjuvant Chemotherapy Failure

Int J Mol Sci. 2023 Nov 1;24(21):15869. doi: 10.3390/ijms242115869.

Authors

Bence Nagy-Mikó¹, Orsolya Németh-Szatmári¹, Réka Faragó-Mészáros¹, Aliz Csókási^{1

2}, Bence Bognár¹, Nóra Ördög², Barbara N Borsos², Hajnalka Majoros^{2

3}, Zsuzsanna Ujfaludi^{2

3}, Orsolya Oláh-Németh², Aliz Nikolényi⁴, Ágnes Dobi⁴, Renáta Kószó⁴, Dóra Sántha⁴, György Lázár⁵, Zsolt Simonka⁵, Attila Paszt⁵, Katalin Ormándi⁶, Tibor Pankotai^{2

3

7}, Imre M Boros¹, Zoltán Villányi¹, András Vörös²

Affiliations

¹ Department of Biochemistry and Molecular Biology, University of Szeged, 52 Középfasor, H-6726 Szeged, Hungary.
² Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Állomás utca 1, H-6725 Szeged, Hungary.
³ Competence Centre of the Life Sciences Cluster of the Centre of Excellence for Interdisciplinary Research, Development and Innovation, University of Szeged, Dugonics tér 13, H-6720 Szeged, Hungary.
⁴ Department of Oncotherapy, Albert Szent-Györgyi Health Centre, University of Szeged, 12 Korányi Fasor, H-6720 Szeged, Hungary.
⁵ Department of Surgery, Albert Szent-Györgyi Health Centre, University of Szeged, 8 Semmelweis Street, H-6725 Szeged, Hungary.
⁶ Department of Radiology, Albert Szent-Györgyi Health Centre, University of Szeged, 6 Semmelweis Street, H-6725 Szeged, Hungary.
⁷ Genome Integrity and DNA Repair Core Group, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), University of Szeged, Budapesti út 9, H-6728 Szeged, Hungary.

Abstract

We aimed to investigate the contribution of co-translational protein aggregation to the chemotherapy resistance of tumor cells. Increased co-translational protein aggregation reflects altered translation regulation that may have the potential to buffer transcription under genotoxic stress. As an indicator for such an event, we followed the cytoplasmic aggregation of RPB1, the aggregation-prone largest subunit of RNA polymerase II, in biopsy samples taken from patients with invasive carcinoma of no special type. RPB1 frequently aggregates co-translationally in the absence of proper HSP90 chaperone function or in ribosome mutant cells as revealed formerly in yeast. We found that cytoplasmic foci of RPB1 occur in larger sizes in tumors that showed no regression after therapy. Based on these results, we propose that monitoring the cytoplasmic aggregation of RPB1 may be suitable for determining-from biopsy samples taken before treatment-the effectiveness of neoadjuvant chemotherapy.

Keywords: CCR4-NOT; RNAPII; RPB1; aggregation; assemblysomes; condensates; epirubicin; invasive carcinoma of no special type; neoadjuvant therapy.

MeSH terms

Humans
Neoadjuvant Therapy
Protein Aggregates
RNA Polymerase II* / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins* / metabolism

Substances

RNA Polymerase II
Protein Aggregates
Saccharomyces cerevisiae Proteins
RPB1 protein, S cerevisiae

Grants and funding

This work was supported by grants OTKA-142961, GINOP-2.3.2-15-2016-00020, and GINOP-2.3.2-15-2016-00038, as well as by ÚNKP-19-4-SZTE-118, ÚNKP-21-5-595-SZTE (Z.V.) GINOP-2.2.1-15-2017-00052, 2019-1.1.1-PIACI-KFI-2019-00080, ÚNKP-21-5-SZTE-563, ÚNKP-22-5-SZTE-318 (T.P.), ÚNKP-23-3-SZTE-311 (N.Ö.), NKFI-FK 132080, NTP-NFTÖ-21-B-0043 (B.N.B.) from the Hungarian National Research, Development and Innovation Office. Further support was provided by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/902/19 for Z.V. and BO/27/20 for T.P.). The project has received funding from the EU’s Horizon 2020 research and innovation program under grant agreement No. 739593. Project no. TKP-2021-EGA-05 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, funded by the TKP2021-EGA grant program (T.P.). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.