MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration

Abstract

BackgroundMyeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design.MethodsMEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells. Western blot and real-time qPCR (quantitative Polymerase Chain Reaction) was performed to examine the protein and mRNA levels of MEIS1. Cell proliferation, survival, in vitro migration and invasion were tested by MTT, colony formation, soft-agar, transwell (in vitro invasion/migration) assays, and tumor in vivo growthwas measured on nude mice model. In addition, flow-cytometry analysis was used to detect cell cycle arrest or non-apoptotic cell death of ccRCC cells induced by MEIS1.ResultsMEIS1 exhibits a decreased expression in ccRCC cell lines than that in non-tumor cell lines. MEIS1 overexpression inhibits ccRCC cells proliferation and induces G1/S arrest concomitant with marked reduction of G1/S transition regulators, Cyclin D1 and Cyclin A. Moreover, MEIS1-1 overexpression also induces non-apoptotic cell death of ccRCC cells via decreasing the levels of pro-survival regulators Survivin and BCL-2. Transwell migration assay (TMA) shows that MEIS1 attenuates in vitro invasion and migration of ccRCC cells with down-regulated epithelial-mesenchymal transition (EMT) process. Further, in nude mice model, MEIS1 inhibits the in vivo growth of Caki-1 cells.ConclusionsBy investigating the role of MEIS1 in ccRCC cells’ survival, proliferation, anchorage-independent growth, cell cycle progress, apoptosis and metastasis, in the present work, we propose that MEIS1 may play an important role in clear cell renal cell carcinoma (ccRCC) development.

MEIS-1 level in unresectable hepatocellular carcinoma can predict the post-treatment outcomes of radiofrequency ablation

“…A previous study reported higher expression of MEIS-1 in healthy prostate tissues than in prostate carcinoma tissues, and concluded that MEIS-1 may serve as a predictive biomarker of prostate cancer prognosis [ 21 ]. Similar studies reported that MEIS-1 is a suppressor of non-small-cell lung cancer, esophageal squamous cell carcinomas and clear cell renal cell carcinomas [ 14 , 22 – 25 ]. A recent paper reported that MEIS-1's expression level can predict treatment outcome in HCC patients [ 26 ].…”

“…For example, aberrant expression of MEIS-1 promoted the development of acute myeloid leukemia [ 15 – 19 , 35 ]. However, MEIS-1 has been reported as a negative regulator of some other cancers, such as non-small-cell lung cancer, esophageal squamous cell carcinomas, clear cell renal cell carcinomas and prostate cancer [ 22 – 25 ]. In these studies, the authors proposed that MEIS-1 inhibits tumor cell proliferation and induces cell cycle arrest [ 22 – 25 ].…”

“…However, MEIS-1 has been reported as a negative regulator of some other cancers, such as non-small-cell lung cancer, esophageal squamous cell carcinomas, clear cell renal cell carcinomas and prostate cancer [ 22 – 25 ]. In these studies, the authors proposed that MEIS-1 inhibits tumor cell proliferation and induces cell cycle arrest [ 22 – 25 ]. In the present study, the patients with high MEIS-1 expression show better post-RFA outcomes than those with low MEIS-1 expression.…”

Transition from normal to cancerous cell by precancerous niche (PCN) induced chronic cell-matrix stress

“…Splice variants of Meis1 containing Meis1a and Meis1b found in human and mice and two new Meis1d transcripts were found with 27 kD weight (Meis1 27 ) in cytoplasm of proximal colon epithelial cells and the Meis1 32 kD variant (Meis1 32 ) in the nuclei of non-epithelial cells in the stomach and colon; finding various Meis1 variants in different cell types and subcellular compartments [64]. This may explain the contradictory findings that Meis1D, the homeodomain-less splice variant of Meis1, is found to inhibit gastric [65] and clear renal cell carcinogenesis [66], or to be downregulated in colorectal carcinomas, suggesting that Meis1D is a tumor suppressor [64].…”

“…PREP1 has been associated with induction of cell transition and cancer spread through the TGF-b/ SMAD3 pathway in non-small cell lung carcinoma (NSCLC) [71]. As Meis1 was reported to induce G1/2 arrests and non-apoptotic cell death through decreased levels of Survivin and B-cell lymphoma 2 (Bcl-2) [66], its non-oncogene effect might be a matter of concentration which, in turn, argues in favor of the disruption-of-homeostasis concept in carcinogenesis. Meis1 associated cell growth promotion is directly linked to RB1 cell-cycle signaling [72].…”