MicroRNA-20b Promotes Cell Growth Of Breast Cancer Cells Partly Via Targeting PTEN

Breast cancer is the most common malignancy in the world,and is the leading cause of cancer deaths in women.At present,the factors such as the etiology and complexity of breast cancer have challenged the prevention and treatment of breast cancer.Breast cancer tumorigenesis can be described as a multi-step process.In this process,normal cells undergo malignant transformation and turn into fully developed tumor through the accumulation of genetic and epigenetic changes.Although changes in many oncogenes and tumor suppressor genes associated with breast cancer have been found,the molecular mechanisms that maintain the malignant proliferation of tumor cells are still poorly understand.MicroRNAs(miRNAs)are highly conservative,endogenous,small non-coding RNAs that play important roles in multiple biological processes.Micro RNA caused the degradation or translation inhibition of target mRNA by completely or not fully complemented bind to the 3 ’UTR of the target gene mRNA,which is an important regulatory factor in the post-transcriptional level.It is reported that mir-20b is involved in the development of breast cancer,but its mechanism is still unclear and needs further discussion.The aim of this study is to explicit the molecular mechanism of miR-20b underlying breast cancer tumorigenesis.In this study,compared with adjacent normal tissues and normal cell lines,we found that mir-20b was overexpressed in human breast cancer tissues and cell lines.We indentified the known tumor suppressor PTEN as the downstream target of mir-20b.Than we use luciferase assays to confirmed that miR-20b could directly bind to the 3’ untranslated region(UTR)of PTEN and suppress translation.Up and down regulation of miR-20b expression changed PTEN protein level but not its mRNA expression both in ZR-75-30 and MCF-7 breast cancer cells,indicating miR-20b regulates PTEN gene expression at the posttranscriptional level.Furthermore,upregulation of miR-20b can significantly promoted the proliferation,colony formation and DNA synthesis of ZR-75-30 and MCF-7 breast cancer cells.On the contrary,knockdown of miR-20b expression could inhibit the growth of breast cancer cells in vitro and in vivo.In the above experiments,we found that the dysregulation of mir-20b plays a critical role in the breast cancer tumorigenesis,at least in part by targeting tumor suppressor PTEN.This microRNA may serve as a potential diagnostic marker and therapeutic target for breast cancer.