Etude du facteur épigénétique RINF dans les cellules de l’écosystème tumoral

Functional study of the epigenetic factor RINF (alias CXXC5) in tumor ecosystem

Scientific background
Our group has identified the CXXC5 gene and demonstrated that this gene encodes a Retinoid-Inducible Nuclear Factor (RINF) [1]. We have demonstrated its role during normal human hematopoiesis (granulopoiesis [1] and erythropoiesis [2]).

illustration RINF projet Pendino

We have also shown that RINF/CXXC5 mRNA expression is an adverse prognostic marker in acute myeloid leukemia [3, 4, 6], breast cancer [5, 7], and proposed this factor as a challenging therapeutic target in cancer [3, 4]. Moreover, this gene is also expressed in particular myeloid and lymphoid cells and its functional contribution to these immune cells remains to establish in normal and tumor microenvironment contexts.

Illustration RINF dans projet recherche Pendino

At the molecular level, RINF protein contains a CXXC zinc finger motif that is similar to the one harbored by TET1 and TET3, two master epigenetic factors responsible for genome-wide CpG 5’-hydroxymethylation (5hmC) together with TET2 (that lacks this CXXC-motif). Thus, RINF could interfere with TET-activities and 5hmC [8, 9, 10 and data not shown]. We hypothesize that such putative epigenetic modifications could alter the functionality of immune and/or tumor cells.
Objectives :
By using gain and loss-of-function experiments (lentiviral vectors) with human cells (primary cells or cell lines), and animal models (conditional and constitutive Rinf knockout mouse), our aim is to further characterize the role of Rinf in blood, immune and tumor cells. We also study the consequence of Rinf gene invalidation on tumor development in vivo. Spontaneous or transplanted mammary tumor cells model are used to distinguish tumor cell intrinsic protumoral functions of Rinf from the one of the tumor microenvironment (such as tumor-infiltrating immune cells).

alignement séquences RINF projet Pendino