竞争性内源RNA（ceRNAs）通过调节microRNAs的生物活性在肿瘤的发生发展中发挥重要作用，ceRNAs在肿瘤转移中的作用机制研究是目前国内外研究热点之一。本课题组先前研究证实了miR-125b通过靶向STARD13促进上皮间质转化的发生从而提高乳腺癌转移能力。本项目进一步提出miR-125b有可能通过ceRNAs网络调控机制对乳腺癌转移起重要作用。为此，本项目拟开展以下研究：1）采用生物信息学方法、免疫共沉淀结合高通量测序等技术并结合临床样本分析确证miR-125b相关ceRNAs调控网络的存在；2）应用活细胞工作站、近红外活体成像等技术在体内外探讨miR-125b 相关ceRNAs网络对乳腺癌转移的调控作用；3）通过荧光素酶报告法、重组质粒构建等研究方法深入阐述microRNAs与ceRNAs网络对乳腺癌转移调控作用的新机制；从而为恶性肿瘤的临床诊断与治疗提供新的靶点。

Competing Endogenous RNAs (ceRNAs) play a critical role in tumorigenesis by regulating the bioactivities of microRNAs. The underlying mechanism of ceRNAs' regulative effects on cancer metastasis is one of the most heated topics. We previously proved that miR-125b promotes epithelial-mesenchymal transition (EMT) by targeting STARD13. Therefore miR-125b increases the metastatic ability of breast cancer cells. In this study, we furtherly assume that miR-125b affects breast cancer metastasis through ceRNA crosstalk. To prove this hypothesis, our team carries out the following research: 1) The existence of miR-125b-related ceRNA crosstalk is validated by utilizing bioinformatics and co-immunoprecipitation high-throughput sequencing. 2) Regulative effect of miR-125b-related ceRNAs crosstalk is investigated with the help of live cell station and near-infrared in vivo imaging. 3) By utilizing luciferase assay and recombinant plasmid, the new mechanisms of the interaction between microRNAs and ceRNA crosstalk, as well as its regulative effect on the metastasis of breast cancer, is in-depthly demonstrated. In this way, we make efforts to discover a new potential target for clinical diagnosis and treatment of cancer.

ceRNA理论是基于近年来关于RNA转录体之间相互对话的研究而提出的。近年来国内外已经有很多研究证实竞争性内源RNA（ceRNA）网络与肿瘤的发生及发展有着密切的关系。我们研究研究发现miR-125b相关ceRNAs网络可通过抑制乳腺癌EMT过程进而抗乳腺癌转移。其中STARD13及其ceRNAs（CDH5,HOXD1以及HOXD10）可抑制乳腺癌转移，而相关的miRNAs（miR-125b，miR-10b及miR-9）可促进乳腺癌转移。该项目采用小动物活体成像以及活细胞工作站，结合分子生物学手段，可视、动态的观察了该ceRNAs网络中各个成分对乳腺癌转移能力的调控作用。并结合临床样本进一步探讨了该ceRNAs网络抑制乳腺癌转移的具体机制。在一定程度上揭示了该ceRNAs网络在乳腺癌转移过程中的科学内涵，为深入挖掘乳腺癌转移的机制及其开发治疗乳腺癌的靶点提供了理论依据。