Effect of myeloid ecotropic viral integration site (MEIS) family genes on tumor microenvironment remodeling and its potential therapeutic effect

Abstract

Background: The myeloid ecotropic viral integration site (MEIS) family of genes is related to the occurrence, development, and outcome of many cancers. However, its role in the immune and tumor microenvironment (TME) is unclear. This study explored the relationship between the expression of MEIS genes and patient survival, immune subtypes, TME, tumor stem cell correlation, and drug sensitivity in cancer. Methods: We used The Cancer Genome Atlas pan-cancer data to analyze the expression of the MEIS family genes. Kaplan-Meier analysis and univariate Cox proportional hazard regression model were used to detect the relationship between gene expression and overall survival. Analysis of variance was used to explore the relationship between the MEIS family and the immune components in the tumor, and the ESTIMATE algorithm was used to calculate the proportion and level of tumor-infiltrating immune cells. Spearman and Pearson's correlation tests were carried out to detect the relationship between MEIS and the characteristics of tumor stem cells and drug sensitivity. Results: The MEIS family of genes shows different expression profiles in different cancers, with substantial inter-and intra-cancer heterogeneity. Among them, MEIS3 was upregulated in most cancers, whereas MEIS2 was downregulated. The change in MEIS gene expression was usually related to overall survival, but whether a member of the MEIS family was a risk factor or a protective factor was cancer-dependent. Immune component analysis suggested that the role of MEIS genes in promoting or inhibiting cancer may be related to different degrees of immune silencing. Further, there were varying degrees of correlation between MEIS gene expression and cancer cell stemness characteristics. It was also found that MEIS genes, especially MEIS1 and MEIS2, may be related to chemotherapy resistance. Conclusions: We explored the expression, prognostic relationship, molecular characteristics, and effects on immunity and TME of the MEIS gene family in cancer. Our results suggest that MEIS members should be studied as independent entities in different types of cancer. The MEIS gene family may be a potential target for cancer therapy, but further experiments are needed to confirm this.

Transcription Factor ELF1 Modulates Cisplatin Sensitivity in Prostate Cancer by Targeting MEIS Homeobox 2

“…In prostate cancer, MEIS2 has been reported as a potential tumor suppressor . Previous study also illustrated that MEIS2 may be associated with chemoresistance and exert effect on the sensitivity or resistance of tumor cells to drug therapy and could be a therapeutic target to overcome drug resistance or enhance drug sensitivity . Our study demonstrated that MEIS2 was notably lowly expressed in prostate cancer tissues and cells.…”

“…8 Previous study also illustrated that MEIS2 may be associated with chemoresistance and exert effect on the sensitivity or resistance of tumor cells to drug therapy and could be a therapeutic target to overcome drug resistance or enhance drug sensitivity. 37 Our study demonstrated that MEIS2 was notably lowly expressed in prostate cancer tissues and cells. After overexpression of MEIS2, PC-3 cell viability was notably attenuated, and the number of cells in the S phase decreased, while that in the G0/ G1 phase increased.…”

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance

“…The constitutive NF-κB signaling circuit drives the expression of a group of stem cell transcription factors, including Twist2, Sox2, Oct4, and Nanog, to promote the cancer stem cell-like characteristics and tumorigenicity of CRPC cells [22]. Consistently, a recent report supported the role of MEIS2 in cancer cell stemness [28]. In addition, it has been reported that high mobility group box 1 protein (HMGB1) activates the NF-κB signaling pathway via interaction with and binding to TNFR1 in CRPC cells [29].…”

Evaluation of the HOXA9 and MEIS1 genes as a potential biomarker in adult acute myeloid leukemia

“…This discrepancy may be caused by the small size of our sample. Additionally, the MEIS1 gene expression behavior in malignant cells is influenced by many factors, including the immune status of the patients and the tumor microenvironment [33].…”