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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Myeloid 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.

Methods

MEIS1 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.

Results

MEIS1 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.

Conclusions

By 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.

Related collections

Most cited references 25

Record: found
Abstract: found
Article: not found

Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy.

Yan Ping Yu, Douglas Landsittel, Ling Jing … (2004)

The incidence of prostate cancer is frequent, occurring in almost one-third of men older than 45 years. Only a fraction of the cases reach the stages displaying clinical significance. Despite the advances in our understanding of prostate carcinogenesis and disease progression, our knowledge of this disease is still fragmented. Identification of the genes and patterns of gene expression will provide a more cohesive picture of prostate cancer biology. In this study, we performed a comprehensive gene expression analysis on 152 human samples including prostate cancer tissues, prostate tissues adjacent to tumor, and organ donor prostate tissues, obtained from men of various ages, using the Affymetrix (Santa Clara, CA) U95a, U95b, and U95c chip sets (37,777 genes and expression sequence tags). Our results confirm an alteration of gene expression in prostate cancer when comparing with nontumor adjacent prostate tissues. However, our study also indicates that the gene expression pattern in tissues adjacent to cancer is so substantially altered that it resembles a cancer field effect. We also found that gene expression patterns can be used to predict the aggressiveness of prostate cancer using a novel model.

0 comments Cited 245 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Meis1 regulates postnatal cardiomyocyte cell cycle arrest.

Ahmed Mahmoud, Fatih Kocabas, Shalini Muralidhar … (2013)

The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation. However, this regenerative capacity is lost by postnatal day 7 and the mechanisms of cardiomyocyte cell cycle arrest remain unclear. The homeodomain transcription factor Meis1 is required for normal cardiac development but its role in cardiomyocytes is unknown. Here we identify Meis1 as a critical regulator of the cardiomyocyte cell cycle. Meis1 deletion in mouse cardiomyocytes was sufficient for extension of the postnatal proliferative window of cardiomyocytes, and for re-activation of cardiomyocyte mitosis in the adult heart with no deleterious effect on cardiac function. In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration. Finally, we show that Meis1 is required for transcriptional activation of the synergistic CDK inhibitors p15, p16 and p21. These results identify Meis1 as a critical transcriptional regulator of cardiomyocyte proliferation and a potential therapeutic target for heart regeneration.

0 comments Cited 224 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice.

J Moskow, F Bullrich, K. Huebner … (1995)

Leukemia results from the accumulation of multiple genetic alterations that disrupt the control mechanisms of normal growth and differentiation. The use of inbred mouse strains that develop leukemia has greatly facilitated the identification of genes that contribute to the neoplastic transformation of hematopoietic cells. BXH-2 mice develop myeloid leukemia as a result of the expression of an ecotropic murine leukemia virus that acts as an insertional mutagen to alter the expression of cellular proto-oncogenes. We report the isolation of a new locus, Meis1, that serves as a site of viral integration in 15% of the tumors arising in BXH-2 mice. Meis1 was mapped to a distinct location on proximal mouse chromosome 11, suggesting that it represents a novel locus. Analysis of somatic cell hybrids segregating human chromosomes allowed localization of MEIS1 to human chromosome 2p23-p12, in a region known to contain translocations found in human leukemias. Northern (RNA) blot analysis demonstrated that a Meis1 probe detected a 3.8-kb mRNA present in all BXH-2 tumors, whereas tumors containing integrations at the Meis1 locus expressed an additional truncated transcript. A Meis1 cDNA clone that encoded a novel member of the homeobox gene family was identified. The homeodomain of Meis1 is most closely related to those of the PBX/exd family of homeobox protein-encoding genes, suggesting that Meis1 functions in a similar fashion by cooperative binding to a distinct subset of HOX proteins. Collectively, these results indicate that altered expression of the homeobox gene Meis1 may be one of the events that lead to tumor formation in BXH-2 mice.

0 comments Cited 45 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Jie Zhu: jie-zhu_Urology@hotmail.com

Liang Cui: cui_leon@sina.com

Axiang Xu: xu_axiang@foxmail.com

Xiaotao Yin: yxtfwy@163.com

Fanglong Li: 15210253018@163.com

Jiangping Gao: jpgao@163.com

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 7 March 2017

Publication date PMC-release: 7 March 2017

Publication date Collection: 2017

Volume: 17

Electronic Location Identifier: 176

Affiliations

[1 ]ISNI 0000 0004 1761 8894, GRID grid.414252.4, Department of Urology, , Chinese PLA Medical School/Chinese PLA General Hospital, ; Beijing, 100853 People’s Republic of China

[2 ]ISNI 0000 0001 2256 9319, GRID grid.11135.37, Department of Urology, , Civil Aviation General Hospital/Civil Aviation Medical College of Peking University, ; Beijing, 100123 People’s Republic of China

Article

Publisher ID: 3155

DOI: 10.1186/s12885-017-3155-2

PMC ID: 5341457

PubMed ID: 28270206

SO-VID: 4fd0e634-d4e6-4212-b953-05e6ef7afd24

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 27 January 2016

Date accepted : 23 February 2017

Funding

Funded by: Chinese Government

Award ID: the National Natural Science Foundation of China (No. 81100483)

Award Recipient : Jiangping Gao

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: meis1,clear cell renal cell carcinoma,proliferation,in vitro invasion or migration

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: meis1, clear cell renal cell carcinoma, proliferation, in vitro invasion or migration

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

Read this article at

Abstract

Background

Methods

Results

Conclusions

Related collections

Cancer Immunotherapy

Most cited references 25

Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy.

Meis1 regulates postnatal cardiomyocyte cell cycle arrest.

Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice.

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 315

Cited by 11

Most referenced authors 1,068