Enforced expression of miR-101 inhibits prostate cancer cell growth by modulating the COX-2 pathway in vivo

Yubin Hao, Xinbin Gu, Yuan Zhao, Stephen Greene, Wei Sha, Duane T. Smoot, Joseph Califano, Tzyy Choou Wu, Xiaowu Pang

Research output: Contribution to journalArticle

Abstract

It is commonly agreed that there is an association of chronic inflammation with tumorigenesis. COX-2, a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth; thus, overexpression of COX-2 is often found in tumor tissues. Therefore, a better understanding of the regulatory mechanism(s) of COX-2 could lead to novel targeted cancer therapies. In this study, we investigated the mechanism of microRNA-101 (miR-101)-regulated COX-2 expression and the therapeutic potential of exogenous miR-101 for COX-2-associated cancer. A stably expressing exogenous miR-101 prostate cancer cell line (BPH1CmiR101) was generated by using lentiviral transduction as a tool for in vitro and in vivo studies. We found that miR-101 inhibited COX-2 posttranscriptional expression by directly binding to the 3′-untranslated region (3′-UTR) of COX-2 mRNA. The regulatory function of miR-101 was also confirmed by using antisense DNA. As a result, exogenous miR-101 is able to effectively suppress the growth of cultured prostate cancer cells and prostate tumor xenografts. The average tumor weight was significantly lower in the BPH1CmiR101 group (0.22 g) than the BPH1Cvec group (0.46 g). Expression levels of the cell growth regulators, such as cyclin proteins, PCNA (proliferating cell nuclear antigen), EGFR (epidermal growth factor receptor), were also studied. In conclusion, COX-2 is a direct target in miR-101 regulation of posttranscription. Exogenous miR-101 suppresses the proliferation and growth of prostate cancer cells in vitro and in vivo. These data suggest that exogenous miR-101 may provide a new cancer therapy by directly inhibiting COX-2 expression.

Original languageEnglish (US)
Pages (from-to)1073-1083
Number of pages11
JournalCancer Prevention Research
Volume4
Issue number7
DOIs
StatePublished - Jul 2011

Fingerprint

MicroRNAs
Prostatic Neoplasms
Growth
Neoplasms
Antisense DNA
Inflammation
Cyclins
Proliferating Cell Nuclear Antigen
3' Untranslated Regions
Tumor Burden
Epidermal Growth Factor Receptor
Heterografts
Prostaglandins
Carcinogenesis
Therapeutics
Cell Proliferation
Cell Line
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Enforced expression of miR-101 inhibits prostate cancer cell growth by modulating the COX-2 pathway in vivo. / Hao, Yubin; Gu, Xinbin; Zhao, Yuan; Greene, Stephen; Sha, Wei; Smoot, Duane T.; Califano, Joseph; Wu, Tzyy Choou; Pang, Xiaowu.

In: Cancer Prevention Research, Vol. 4, No. 7, 07.2011, p. 1073-1083.

Research output: Contribution to journalArticle

Hao, Yubin ; Gu, Xinbin ; Zhao, Yuan ; Greene, Stephen ; Sha, Wei ; Smoot, Duane T. ; Califano, Joseph ; Wu, Tzyy Choou ; Pang, Xiaowu. / Enforced expression of miR-101 inhibits prostate cancer cell growth by modulating the COX-2 pathway in vivo. In: Cancer Prevention Research. 2011 ; Vol. 4, No. 7. pp. 1073-1083.
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abstract = "It is commonly agreed that there is an association of chronic inflammation with tumorigenesis. COX-2, a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth; thus, overexpression of COX-2 is often found in tumor tissues. Therefore, a better understanding of the regulatory mechanism(s) of COX-2 could lead to novel targeted cancer therapies. In this study, we investigated the mechanism of microRNA-101 (miR-101)-regulated COX-2 expression and the therapeutic potential of exogenous miR-101 for COX-2-associated cancer. A stably expressing exogenous miR-101 prostate cancer cell line (BPH1CmiR101) was generated by using lentiviral transduction as a tool for in vitro and in vivo studies. We found that miR-101 inhibited COX-2 posttranscriptional expression by directly binding to the 3′-untranslated region (3′-UTR) of COX-2 mRNA. The regulatory function of miR-101 was also confirmed by using antisense DNA. As a result, exogenous miR-101 is able to effectively suppress the growth of cultured prostate cancer cells and prostate tumor xenografts. The average tumor weight was significantly lower in the BPH1CmiR101 group (0.22 g) than the BPH1Cvec group (0.46 g). Expression levels of the cell growth regulators, such as cyclin proteins, PCNA (proliferating cell nuclear antigen), EGFR (epidermal growth factor receptor), were also studied. In conclusion, COX-2 is a direct target in miR-101 regulation of posttranscription. Exogenous miR-101 suppresses the proliferation and growth of prostate cancer cells in vitro and in vivo. These data suggest that exogenous miR-101 may provide a new cancer therapy by directly inhibiting COX-2 expression.",
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