MicroRNA-143/145Play A Tumor Suppressor Role In Breast Cancer By Targeting Of ErbB-3

Breast cancer has a high incidence in worldwild. There are many studies proved the importance of tyrosine kinase receptor family in breast cancer. For a long time, people pay more attention to ErbB-2in breast cancer, but a lot of evidence also proof ErbB-3is important too. MiRNA has been proved to play an important role in breast cancer. We hypothesize that some miRNA may play a tumor suppressor role in breast cancer by targeting of ErbB-3.MicroRNAs (miRNAs) are a class of endogenous non-coding single-stranded RNAs, consisting of nearly22nucleotides in length. They play an important role in regulating gene expression at the post-transcriptional level by base-pairing to the complementary sites on the target mRNAs, thus blocking the translation or triggering the degradation of the target mRNAs.First, we find ErbB-3play an important role in the occurrence and development of breast cancer by literature search. ErbB-3is essential in the proliferation and differentiation of cancer cell. Next, we analyzed some miRNAs which were also reported important in breast cancer by some bioinformatics software, such as TargetScan, PicTar, miRnada. ErbB-3was thought to be regulated by miR-143and miR-145in breast cancer. Secondly, we choice the MCF-7cell lines to be studied, miR-143and miR-145were over-expressed in it. The level of ErbB-3protein was decreased obviously but the mRNA level was stable. Otherwise, when miR-143and miR-145were inhibited, the mRNA was also unchanged but the protein elevated. Thirdly, a luciferase reporter assay was conducted to demonstrate that miR-143and miR-145can directly recognize the3’-UTRs of ErbB-3and mediate the post-transcriptional inhibition of this gene. Fourth, we find that miR-143and miR-145could have an impact on cell proliferation and migrate in MCF-7cells. Fifth, a lentiviral vector which contained overexpress genes of miR-143and miR-145was constructed. A stable transfection cell lines which can expression miR-143and miR-145continued was also maked though the lentiviral vector. We use the stable transfection cell lines and the normal MCF-7cell lines to plant tumor in the armpit of mice respectively. The tumor formed by the stable transfection cell lines was smaller and lighter.These results suggest that ErbB-3could work as an oncogene in the formation and develop of breast cancer by influence the breast cancer cells proliferation and migrate. MiR-143and miR-145could play a tumor suppressor role in breast cancer though negative regulation the ErbB-3gene.The signification of this study is confirmed the relationship between miR-143, miR-145and ErbB-3. We also could further understand the importance of miRNA in breast cancer. As an oncogene, ErbB-3was also studied in breast cancer and regarded as a new therapeutic target. The regulatory relationship between miR-143, miR-145and ErbB-3has an important significance in cancer treatment, such as tumor detection, screening of therapeutic targets, clinical research and development of new drugs.