Oncogenic and tumor suppressor function of MEIS and associated factors

Abstract

MEIS proteins are historically associated with tumorigenesis, metastasis, and invasion in cancer. MEIS and associated PBX-HOX proteins may act as tumor suppressors or oncogenes in different cellular settings. Their expressions tend to be misregulated in various cancers. Bioinformatic analyses have suggested their upregulation in leukemia/lymphoma, thymoma, pancreas, glioma, and glioblastoma, and downregulation in cervical, uterine, rectum, and colon cancers. However, every cancer type includes, at least, a subtype with high MEIS expression. In addition, studies have highlighted that MEIS proteins and associated factors may function as diagnostic or therapeutic biomarkers for various diseases. Herein, MEIS proteins and associated factors in tumorigenesis are discussed with recent discoveries in addition to how they could be modulated by noncoding RNAs or newly developed small-molecule MEIS inhibitors.

The impact of glutamine deprivation on the expression of MEIS3, SPAG4, LHX1, LHX2, and LHX6 genes in ERN1 knockdown U87 glioma cells

“…Furthermore, these changes in MEIS3 gene expression under glutamine deprivation are essentially independent of ERN1 inhibition. There are data indicating that the expression of this gene is up-regulated in glioblastoma as well as in many other tumors (Girgin et al 2020). It is possible that the up-regulation of MEIS3 gene under glutamine deprivation reflects compensatory mechanism connected with decreased proliferation rate of glioma cells under nutrient starvation (Awale et al 2006;Colombo et al 2011;Drogat et al 2007;Kim et al 2010;He et al 2018).…”

“…Moreover, SPAG4 could serve as an independent prognostic factor for glioblastoma patients and might be valuable for the clinical management of these patients (Zhang et al 2021). There are data indicating that MEIS proteins are associated with tumorigenesis, metastasis, and invasion in cancer and may act as tumor suppressors or oncogenes in different cellular settings and that the expression of MEIS3 is upregulated in glioblastoma and many other cancers (Girgin et al 2020). Furthermore, it was also shown that microRNA-202-3p has tumor-suppressive role in the hepatocellular carcinoma through the KDM3A/ HOXA1/MEIS3 pathway because upregulation of this miRNA reduced the growth of human hepatocellular carcinoma cells in vivo (Zhang et al 2020).…”

Charting the Heterogeneity of Colorectal Cancer Consensus Molecular Subtypes using Spatial Transcriptomics

“…4g). The family of MEIS TFs can act as tumor suppressors or oncogenes under different cellular conditions and cancer types and their target genes are widely misregulated in CRC 59 . These results suggest that DCN may influence the transcriptional activity of MEIS1 through the downstream signaling of the SRC kinase family (Fig.…”

MEIS1 in Hematopoiesis and Cancer. How MEIS1-PBX Interaction Can Be Used in Therapy

“…MEIS1 also plays a role in solid tumors; however, in this case the MEIS1 role is contradictory as it may behave as an oncogene or a tumor suppressor. The role of the whole MEIS protein family (MEIS1, MEIS2, and MEIS3) in solid cancers has been recently reviewed by Girgin and colleagues [105]. MEIS1 overexpression in several solid cancers has an important oncogenic function, for example, in breast [106,107], colorectal [108], human esophageal squamous cell [109,110], neuroblastoma [111], ovarian [112], and prostate cancers [113], where its upregulation has been associated to cancer etiology, progression, and increased invasiveness.…”