MicroRNA-214 regulates osteosarcoma survival and growth by directly targeting phosphatase and tensin homolog.

نویسندگان

  • Xuming Wang
  • Jiabing Sun
  • Chunjiang Fu
  • Dewei Wang
  • Zhenggang Bi
چکیده

An increasing number of microRNAs (miRNAs) have been identified as diagnostic and prognostic biomarkers, as well as additional therapeutic tools, in skeletal diseases. Recent studies have established the pathophysiological role of miR‑214, using human osteoporotic bone specimens. However, miR‑214 expression levels and the underlying regulatory mechanism in human osteosarcoma remain unclear. Quantitative polymerase chain reaction (qPCR) was used to examine the expression of miR‑214 in human osteosarcoma tissues and cells. Transfection of the cells with either a miR‑214 expressing‑plasmid, mimic or inhibitor was performed, in order to investigate the role of miR‑214 in osteosarcoma. In this study, miR‑214 was shown to be significantly increased in the majority of 15 examined osteosarcoma tissues and in the Saos‑2 human osteosarcoma cell line. Overexpression of miR‑214 in Saos‑2 cells induced cell proliferation, while inhibition of miR‑214 promoted Saos‑2 cell apoptosis in vitro. Furthermore, ectopic expression of miR‑214 markedly promoted osteosarcoma development in a subcutaneous xenotransplantation model in BALB/c athymic nude mice. The role of miR‑214 in osteocarcinogenesis was further investigated and phosphatase and tensin homolog (PTEN) was determined to be a direct target of miR‑214 in Saos‑2 cells. The proliferation‑promoting effect of PTEN knockdown was similar to that of miR‑214 overexpression. This study revealed that miR‑214 exerted a crucial role in promoting osteosarcoma progression and this suggests that modulation of miR‑214 levels may provide a novel therapeutic approach in cancer treatment.

برای دانلود 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

Inhibition of miR-214 in OS cell lines markedly suppressed cell proliferation, migration and invasion. Phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-214, and ectopic expression of miR-214 inhibited PTEN

MicroRNAs (miRNAs) are a class of small non-coding RNAs, which function as critical gene regulators by targeting mRNAs for translational repression or degradation, and they are essential in cancer development and progression. Several previous studies have indicated that abnormal expression of miRNAs occurs frequently in human osteosarcoma (OS) tissues compared with that of adjacent normal tissu...

متن کامل

Increased expression of microRNA-148a in osteosarcoma promotes cancer cell growth by targeting PTEN

Osteosarcoma is the most common type of primary malignant bone tumor, and deregulated microRNAs (miRNAs or miRs) in osteosarcoma have attracted great attention. In the present study, through miRNA microarray analysis, it was identified that miR-148a expression was significantly increased in osteosarcoma tissues. Increased miR-148a expression was significantly correlated with tumor progression a...

متن کامل

MicroRNA-300 Regulates the Ubiquitination of PTEN through the CRL4BDCAF13 E3 Ligase in Osteosarcoma Cells

Cullins, critical members of the cullin-RING ubiquitin ligases (CRLs), are often aberrantly expressed in different cancers. However, the underlying mechanisms regarding aberrant expression of these cullins and the specific substrates of CRLs in different cancers are mostly unknown. Here, we demonstrate that overexpressed CUL4B in human osteosarcoma cells forms an E3 complex with DNA damage bind...

متن کامل

MicroRNA-1908 is upregulated in human osteosarcoma and regulates cell proliferation and migration by repressing PTEN expression.

Osteosarcoma is a high-grade malignant bone neoplasm. Although the introduction of chemotherapy has reduced its mortality, >50% of patients develop chemoresistance and have an extremely poor prognosis due to pulmonary metastasis. Several molecular pathways contributing to osteosarcoma development and progression have recently been identified. Various studies have addressed the genes involved in...

متن کامل

Costimulation-dependent expression of microRNA-214 increases the ability of T cells to proliferate by targeting Pten.

T cell activation requires signaling through the TCR and costimulatory molecules, such as CD28. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression posttranscriptionally and are also known to be involved in lymphocyte development and function. In this paper, we set out to examine potential roles of miRNAs in T cell activation, using genome-wide expression profiling to iden...

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

برای دانلود 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

عنوان ژورنال:
  • Molecular medicine reports

دوره 10 6  شماره 

صفحات  -

تاریخ انتشار 2014