Regulation of minichromosome maintenance gene family by MicroRNA-1296 and genistein in prostate cancer

Shahana Majid, Altaf A. Dar, Sharanjot Saini, Yi Chen, Varahram Shahryari, Jan Liu, Mohd Saif Zaman, Hiroshi Hirata, Soichiro Yamamura, Koji Ueno, Yuichiro Tanaka, Rajvir Dahiya

Research output: Contribution to journalArticle

Abstract

The minichromosome maintenance (MCM) gene family is essential for DNA replication and is frequently upregulated in various cancers. Here, we examined the role of MCM2 in prostate cancer and the effect of microRNA-1296 (miR-1296), genistein, and trichostatin A (TSA) on the MCM complex. Profiling results showed that expression of MCM genes was higher in tumor samples. Genistein and TSA significantly downregulated the expression of all MCM genes. Genistein, TSA, and small interfering RNA duplexes caused a significant decrease in the S phase of the cell cycle. There was also downregulation of CDT1, CDC7, and CDK2 genes, which govern loading of the MCM complex on chromatin. We also found that miR-1296 was significantly downregulated in prostate cancer samples. In PC3 cells, inhibition of miR-1296 upregulated both MCM2 mRNA and protein, whereas overexpression caused a significant decrease in MCM2 mRNA, protein, and the S phase of the cell cycle. MCM genes are excellent anticancer drug targets because they are essential DNA replication factors that are highly expressed in cancer cells. This is the first report showing anti-MCM effect by miR-1296, genistein, and TSA. TSA is undergoing clinical trials as a prostate cancer treatment but has high toxicity. Genistein, a natural, nontoxic dietary isoflavone, may be an advantageous therapeutic agent for treating prostate cancer. The use of RNA interference is currently being implemented as a gene-specific approach for molecular medicine. The specific downregulation of oncogenes by miR may contribute to novel therapeutic approaches in the treatment of prostate cancer.

Original languageEnglish (US)
Pages (from-to)2809-2818
Number of pages10
JournalCancer Research
Volume70
Issue number7
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

Fingerprint

trichostatin A
Genistein
MicroRNAs
Prostatic Neoplasms
Maintenance
Genes
Down-Regulation
DNA Replication
S Phase
Cell Cycle
Molecular Medicine
Neoplasms
Messenger RNA
Isoflavones
Protein S
RNA Interference
Oncogenes
Small Interfering RNA
Chromatin
Clinical Trials

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Majid, S., Dar, A. A., Saini, S., Chen, Y., Shahryari, V., Liu, J., ... Dahiya, R. (2010). Regulation of minichromosome maintenance gene family by MicroRNA-1296 and genistein in prostate cancer. Cancer Research, 70(7), 2809-2818. https://doi.org/10.1158/0008-5472.CAN-09-4176

Regulation of minichromosome maintenance gene family by MicroRNA-1296 and genistein in prostate cancer. / Majid, Shahana; Dar, Altaf A.; Saini, Sharanjot; Chen, Yi; Shahryari, Varahram; Liu, Jan; Zaman, Mohd Saif; Hirata, Hiroshi; Yamamura, Soichiro; Ueno, Koji; Tanaka, Yuichiro; Dahiya, Rajvir.

In: Cancer Research, Vol. 70, No. 7, 01.04.2010, p. 2809-2818.

Research output: Contribution to journalArticle

Majid, S, Dar, AA, Saini, S, Chen, Y, Shahryari, V, Liu, J, Zaman, MS, Hirata, H, Yamamura, S, Ueno, K, Tanaka, Y & Dahiya, R 2010, 'Regulation of minichromosome maintenance gene family by MicroRNA-1296 and genistein in prostate cancer', Cancer Research, vol. 70, no. 7, pp. 2809-2818. https://doi.org/10.1158/0008-5472.CAN-09-4176
Majid, Shahana ; Dar, Altaf A. ; Saini, Sharanjot ; Chen, Yi ; Shahryari, Varahram ; Liu, Jan ; Zaman, Mohd Saif ; Hirata, Hiroshi ; Yamamura, Soichiro ; Ueno, Koji ; Tanaka, Yuichiro ; Dahiya, Rajvir. / Regulation of minichromosome maintenance gene family by MicroRNA-1296 and genistein in prostate cancer. In: Cancer Research. 2010 ; Vol. 70, No. 7. pp. 2809-2818.
@article{2f42719b1e054227a1c1657a1c204ea9,
title = "Regulation of minichromosome maintenance gene family by MicroRNA-1296 and genistein in prostate cancer",
abstract = "The minichromosome maintenance (MCM) gene family is essential for DNA replication and is frequently upregulated in various cancers. Here, we examined the role of MCM2 in prostate cancer and the effect of microRNA-1296 (miR-1296), genistein, and trichostatin A (TSA) on the MCM complex. Profiling results showed that expression of MCM genes was higher in tumor samples. Genistein and TSA significantly downregulated the expression of all MCM genes. Genistein, TSA, and small interfering RNA duplexes caused a significant decrease in the S phase of the cell cycle. There was also downregulation of CDT1, CDC7, and CDK2 genes, which govern loading of the MCM complex on chromatin. We also found that miR-1296 was significantly downregulated in prostate cancer samples. In PC3 cells, inhibition of miR-1296 upregulated both MCM2 mRNA and protein, whereas overexpression caused a significant decrease in MCM2 mRNA, protein, and the S phase of the cell cycle. MCM genes are excellent anticancer drug targets because they are essential DNA replication factors that are highly expressed in cancer cells. This is the first report showing anti-MCM effect by miR-1296, genistein, and TSA. TSA is undergoing clinical trials as a prostate cancer treatment but has high toxicity. Genistein, a natural, nontoxic dietary isoflavone, may be an advantageous therapeutic agent for treating prostate cancer. The use of RNA interference is currently being implemented as a gene-specific approach for molecular medicine. The specific downregulation of oncogenes by miR may contribute to novel therapeutic approaches in the treatment of prostate cancer.",
author = "Shahana Majid and Dar, {Altaf A.} and Sharanjot Saini and Yi Chen and Varahram Shahryari and Jan Liu and Zaman, {Mohd Saif} and Hiroshi Hirata and Soichiro Yamamura and Koji Ueno and Yuichiro Tanaka and Rajvir Dahiya",
year = "2010",
month = "4",
day = "1",
doi = "10.1158/0008-5472.CAN-09-4176",
language = "English (US)",
volume = "70",
pages = "2809--2818",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

TY - JOUR

T1 - Regulation of minichromosome maintenance gene family by MicroRNA-1296 and genistein in prostate cancer

AU - Majid, Shahana

AU - Dar, Altaf A.

AU - Saini, Sharanjot

AU - Chen, Yi

AU - Shahryari, Varahram

AU - Liu, Jan

AU - Zaman, Mohd Saif

AU - Hirata, Hiroshi

AU - Yamamura, Soichiro

AU - Ueno, Koji

AU - Tanaka, Yuichiro

AU - Dahiya, Rajvir

PY - 2010/4/1

Y1 - 2010/4/1

N2 - The minichromosome maintenance (MCM) gene family is essential for DNA replication and is frequently upregulated in various cancers. Here, we examined the role of MCM2 in prostate cancer and the effect of microRNA-1296 (miR-1296), genistein, and trichostatin A (TSA) on the MCM complex. Profiling results showed that expression of MCM genes was higher in tumor samples. Genistein and TSA significantly downregulated the expression of all MCM genes. Genistein, TSA, and small interfering RNA duplexes caused a significant decrease in the S phase of the cell cycle. There was also downregulation of CDT1, CDC7, and CDK2 genes, which govern loading of the MCM complex on chromatin. We also found that miR-1296 was significantly downregulated in prostate cancer samples. In PC3 cells, inhibition of miR-1296 upregulated both MCM2 mRNA and protein, whereas overexpression caused a significant decrease in MCM2 mRNA, protein, and the S phase of the cell cycle. MCM genes are excellent anticancer drug targets because they are essential DNA replication factors that are highly expressed in cancer cells. This is the first report showing anti-MCM effect by miR-1296, genistein, and TSA. TSA is undergoing clinical trials as a prostate cancer treatment but has high toxicity. Genistein, a natural, nontoxic dietary isoflavone, may be an advantageous therapeutic agent for treating prostate cancer. The use of RNA interference is currently being implemented as a gene-specific approach for molecular medicine. The specific downregulation of oncogenes by miR may contribute to novel therapeutic approaches in the treatment of prostate cancer.

AB - The minichromosome maintenance (MCM) gene family is essential for DNA replication and is frequently upregulated in various cancers. Here, we examined the role of MCM2 in prostate cancer and the effect of microRNA-1296 (miR-1296), genistein, and trichostatin A (TSA) on the MCM complex. Profiling results showed that expression of MCM genes was higher in tumor samples. Genistein and TSA significantly downregulated the expression of all MCM genes. Genistein, TSA, and small interfering RNA duplexes caused a significant decrease in the S phase of the cell cycle. There was also downregulation of CDT1, CDC7, and CDK2 genes, which govern loading of the MCM complex on chromatin. We also found that miR-1296 was significantly downregulated in prostate cancer samples. In PC3 cells, inhibition of miR-1296 upregulated both MCM2 mRNA and protein, whereas overexpression caused a significant decrease in MCM2 mRNA, protein, and the S phase of the cell cycle. MCM genes are excellent anticancer drug targets because they are essential DNA replication factors that are highly expressed in cancer cells. This is the first report showing anti-MCM effect by miR-1296, genistein, and TSA. TSA is undergoing clinical trials as a prostate cancer treatment but has high toxicity. Genistein, a natural, nontoxic dietary isoflavone, may be an advantageous therapeutic agent for treating prostate cancer. The use of RNA interference is currently being implemented as a gene-specific approach for molecular medicine. The specific downregulation of oncogenes by miR may contribute to novel therapeutic approaches in the treatment of prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=77950822746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950822746&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-09-4176

DO - 10.1158/0008-5472.CAN-09-4176

M3 - Article

C2 - 20332239

AN - SCOPUS:77950822746

VL - 70

SP - 2809

EP - 2818

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 7

ER -