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

TITLE=MLH1 Deficiency Down-Regulates TLR4 Expression in Sporadic Colorectal Cancer

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.624873

DOI=10.3389/fmolb.2021.624873

ISSN=2296-889X

ABSTRACT=<p>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 <italic>TLR4</italic> mRNA expression and <italic>MLH1</italic> epigenetic silencing status. <italic>In vitro</italic>, the effect of <italic>MLH1</italic> knockdown on <italic>TLR4</italic> expression was quantified by Real Time PCR. TLR4 expression resulted dependent on MMR status and directly correlated to MLH1 expression. <italic>In vitro</italic>, <italic>MLH1</italic> silencing decreased <italic>TLR4</italic> expression. These observations may reflect the better prognosis and the chemoresistance of patients with CRC and MMR defects.</p>