MiRNA203 suppresses the expression of protumorigenic STAT1 in glioblastoma to inhibit tumorigenesis

نویسندگان

  • Chuan He Yang
  • Yinan Wang
  • Michelle Sims
  • Chun Cai
  • Ping He
  • Junming Yue
  • Jinjun Cheng
  • Frederick A. Boop
  • Susan R. Pfeffer
  • Lawrence M. Pfeffer
چکیده

MicroRNAs (miRNAs) play critical roles in regulating cancer cell proliferation, migration, survival and sensitivity to chemotherapy. The potential application of using miRNAs for cancer prognosis holds great promise but miRNAs with predictive value remain to be identified and underlying mechanisms of how they promote or suppress tumorigenesis are not completely understood. Here, we show a strong correlation between miR203 expression and brain cancer patient survival. Low miR203 expression is found in subsets of brain cancer patients, especially glioblastoma. Ectopic miR203 expression in glioblastoma cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon or temozolomide in vitro, and inhibited tumorigenesis in vivo. We further show that STAT1 is a direct functional target of miR203, and miR203 level is negatively correlated with STAT1 expression in brain cancer patients. Knockdown of STAT1 expression mimicked the effect of overexpression of miR203 in glioblastoma cell lines, and inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by IFN or temozolomide in vitro, and inhibited glioblastoma tumorigenesis in vivo. High STAT1 expression significantly correlated with poor survival in brain cancer patients. Mechanistically, we found that enforced miR203 expression in glioblastoma suppressed STAT1 expression directly, as well as that of a number of STAT1 regulated genes. Taken together, our data suggest that miR203 acts as a tumor suppressor in glioblastoma by suppressing the pro-tumorigenic action of STAT1. MiR203 may serve as a predictive biomarker and potential therapeutic target in subsets of cancer patients with low miR203 expression.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The effect of Citrullus colocynthis on the induction of Casp3 and Casp8 gene expression on human Glioblastoma U87 cell line

Introduction: Using in vitro MTT assay and Real-time PCR, the cytotoxicity and cell inhibition mechanism of using Citrullus colocynthis on human glioblastoma U87 cell line was investigated. Methods: The plant extract was extracted using ethanol (70%). To investigate the cytotoxic effects of Citrullus colocynthis extract on U87 cell line, 10 4 cells per well was incubated with different concentr...

متن کامل

The tumor suppressor function of STAT1 in breast cancer

The anti-tumor function of STAT1 through its capacity to control the immune system and promote tumor immune surveillance has been well understood. However, little is known about cell autonomous (i.e., tumor cell-specific) functions of STAT1 in tumor formation. Recent studies have provided strong evidence that STAT1 suppresses mouse mammary gland tumorigenesis by both, immune regulatory and tumo...

متن کامل

Effects of Trichostatin A on the Histone Deacetylases (HDACs), Intrinsic Apoptotic Pathway, p21/Waf1/Cip1, and p53 in Human Neuroblastoma, Glioblastoma, Hepatocellular Carcinoma, and Colon Cancer Cell Lines

Background:  The aberrant and altered patterns of gene expression play an important role in the biology of cancer and tumorigenesis. DNA methylation and histone deacetylation are the most studied epigenetic mechanisms. Histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA) and trichostatin A (TSA) are a group of anticancer compounds for the treatment of solid and hematological canc...

متن کامل

Thiazolidinedione Derivative Suppresses LPS-induced COX-2 Expression and NO Production in RAW 264.7 Macrophages

The present study was designed to investigate the inhibitory effect of 2,4 bis-[(4-ethoxyphenyl)azo] 5-(3-hydroxybenzylidene) thiazolidine-2,4-dione (TZD-OCH2CH3) on the cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in RAW 264.7 cells. The effects of TZD-OCH2CH3 on COX-2 and iNOS mRNA expression in LPS-activated RAW 264.7 cells ...

متن کامل

Thiazolidinedione Derivative Suppresses LPS-induced COX-2 Expression and NO Production in RAW 264.7 Macrophages

The present study was designed to investigate the inhibitory effect of 2,4 bis-[(4-ethoxyphenyl)azo] 5-(3-hydroxybenzylidene) thiazolidine-2,4-dione (TZD-OCH2CH3) on the cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in RAW 264.7 cells. The effects of TZD-OCH2CH3 on COX-2 and iNOS mRNA expression in LPS-activated RAW 264.7 cells ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016