MLH1 Deficiency Down-Regulates TLR4 Expression in Sporadic Colorectal Cancer

Melania Scarpa; Cesare Ruffolo; Andromachi Kotsafti; Fabio Canal; Francesca Erroi; Silvia Basato; Lucia Dall’Agnese; Alain Fiorot; Anna Pozza; Paola Brun; Nicolò Bassi; Angelo Dei Tos; Carlo Castoro; Ignazio Castagliuolo; Marco Scarpa

doi:10.3389/fmolb.2021.624873

Frontiers in Molecular Biosciences (May 2021)

MLH1 Deficiency Down-Regulates TLR4 Expression in Sporadic Colorectal Cancer

Melania Scarpa,
Cesare Ruffolo,
Andromachi Kotsafti,
Fabio Canal,
Francesca Erroi,
Silvia Basato,
Lucia Dall’Agnese,
Alain Fiorot,
Anna Pozza,
Paola Brun,
Nicolò Bassi,
Angelo Dei Tos,
Carlo Castoro,
Ignazio Castagliuolo,
Marco Scarpa

Affiliations

Melania Scarpa: Laboratory of Advanced Translational Research, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Cesare Ruffolo: Clinica Chirurgica I, Azienda Ospedaliera di Padova, Padua, Italy
Andromachi Kotsafti: Laboratory of Advanced Translational Research, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Fabio Canal: Pathology Unit, Treviso Regional Hospital, Treviso, Italy
Francesca Erroi: Department of Surgery, Oncology and Gastroenterology DISCOG, University of Padua, Padua, Italy
Silvia Basato: Department of Surgery, Oncology and Gastroenterology DISCOG, University of Padua, Padua, Italy
Lucia Dall’Agnese: Department of Surgery, Oncology and Gastroenterology DISCOG, University of Padua, Padua, Italy
Alain Fiorot: Department of Surgery, Oncology and Gastroenterology DISCOG, University of Padua, Padua, Italy
Anna Pozza: Department of Surgery, Oncology and Gastroenterology DISCOG, University of Padua, Padua, Italy
Paola Brun: Department of Molecular Medicine DMM, University of Padua, Padua, Italy
Nicolò Bassi: Department of Surgery, Oncology and Gastroenterology DISCOG, University of Padua, Padua, Italy
Angelo Dei Tos: Pathology Unit, Treviso Regional Hospital, Treviso, Italy
Carlo Castoro: Oncological Surgery Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
Ignazio Castagliuolo: Department of Molecular Medicine DMM, University of Padua, Padua, Italy
Marco Scarpa: Clinica Chirurgica I, Azienda Ospedaliera di Padova, Padua, Italy

DOI: https://doi.org/10.3389/fmolb.2021.624873
Journal volume & issue: Vol. 8

Abstract

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Patients with mismatch repair (MMR)-deficient colorectal cancer (CRC) have a more favorable prognosis than patients with tumors with intact MMR. In order to obtain further insights on the reasons for this different outcome, we investigated the interplay between MMR genes and TLR4/MyD88 signaling. The cancer genome atlas (TCGA) databases were selected to predict the differential expression of TLR4 in colon cancer and its correlation with MMR genes. Moreover, the expression of MMR genes and TLR4 was evaluated by immunohistochemistry in 113 CRC samples and a cohort of 63 patients was used to assess TLR4 mRNA expression and MLH1 epigenetic silencing status. In vitro, the effect of MLH1 knockdown on TLR4 expression was quantified by Real Time PCR. TLR4 expression resulted dependent on MMR status and directly correlated to MLH1 expression. In vitro, MLH1 silencing decreased TLR4 expression. These observations may reflect the better prognosis and the chemoresistance of patients with CRC and MMR defects.

Published in Frontiers in Molecular Biosciences

ISSN: 2296-889X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/molecular-biosciences

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