MEIS1 promotes expression of stem cell markers in esophageal squamous cell carcinoma

Abstract

Background: MEIS1 (Myeloid ecotropic viral integration site 1) as a homeobox (HOX) transcription factor plays regulatory roles in a variety of cellular processes including development, differentiation, survival, apoptosis and hematopoiesis, as well as stem cell regulation. Few studies have established pluripotency and self-renewal regulatory roles for MEIS1 in human esophageal squamous cell carcinoma (ESCC), and our aim in this study was to evaluate the functional correlation between MEIS1 and the stemness markers in ESCC patients and cell line KYSE-30. Methods: Expression pattern of MEIS1 and SALL4 gene expression was analyzed in different pathological features of ESCC patients. shRNA in retroviral vector was used for constantly silencing of MEIS1 mRNA in ESCC line (KYSE-30). Knockdown of MEIS1 gene and the expression pattern of selected stemness markers including SALL4, OCT4, BMI-1, HIWI, NANOG, PLK1, and KLF4 were evaluated using real-time PCR. Results: Significant correlations were observed between MEIS1 and stemness marker SALL4 in different early pathological features of ESCC including non-invaded tumors, and the tumors with primary stages of progression. Retroviral knockdown of MEIS1 in KYSE-30 cells caused a noteworthy underexpression of both MEIS1 and major involved markers in stemness state of the cells including SALL4, OCT4, BMI-1, HIWI and KLF4. Conclusions: The results highlight the important potential role of MEIS1 in modulating stemness properties of ESCCs and cells KYSE-30. These findings may confirm the linkage between MEIS1 and self-renewal capacity in ESCC and support probable oncogenic role for MEIS1 in the disease.

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

“…For example, Zargari and colleagues evaluated the expression pattern of MEIS1 in human esophageal squamous cell carcinoma, demonstrating that down-regulated expression of MEIS1 by shRNA decreased the mRNA expression of the most important stem cell markers (such as BMI1, SALL4, OCT4, and KLF4), which can preserve self-renewal and proliferative potential via inhibiting differentiation signaling pathways during cancer initiation and development [114]. However, it has been recently demonstrated that there is an inverse relationship between MYC activity in prostatic cancer, which drives prostate cancer progression, and MEIS1 expression.…”

Comparative Transcriptomic Analysis of the Hematopoietic System between Human and Mouse by Single Cell RNA Sequencing

“…We observed higher activities of GATA1 motifs in MEP, while SPI1 motifs were exclusive in GMP cells of human and mouse. Transcription factor MEIS1 is an HSC marker, and its expression level declines with cell differentiation; it is known to promote expression of stem cell markers in leukemias [ 33 , 34 ]. We observed MEIS1 motifs exclusively activate in LTHSC and MPP of mouse, indicating higher activity in stem cells and early stage of multipotent progenitors.…”

The Concept of “Cancer Stem Cells” in the Context of Classic Carcinogenesis Hypotheses and Experimental Findings

“…However, do they share some common markers that make them a cancer stem cell? As pointed out previously, if the cancer stem cell is derived from a normal organ-specific adult stem cell, and if one marker, namely, the Oct4A gene, is shared by all cancer stem cells, as seems to be indicated by many published papers [60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77], then it would seem that some strategy should be developed to find ways to either shut down this gene in order to force the cells to differentiate or apoptose. In addition, if the connexin genes and functional gap junctions are not found in either the normal stem cells or cancer stem cells, agents that might induce the connexin genes to be expressed could induce either differentiation or apoptosis.…”