循环肿瘤细胞(CTCs)是乳腺癌远处转移的关键细胞群。然而，导致CTCs发生远处转移的分子机制尚不明确。piRNAs被证实是调控肿瘤转移的关键分子。我们的前期研究结果发现：piR-hsa-19386在CTCs中表达下调，且其在原发灶中的表达水平与CTCs的数量呈明显负相关，提示其与CTCs的离巢相关；piR-hsa-19386能抑制乳腺癌CTCs的增值、侵袭和肿瘤干性以及上皮间质转化，提示其调控了CTCs的远处转移；piR-hsa-19386能靶向降解假基因MPRIPP1，释放候选miRNAs靶向MPRIP调控肿瘤转移。为了进一步明确piR-hsa-19386调控乳腺癌CTCs远处转移的作用和机制，申请者拟在CTCs体内外研究模型中，通过干预piR-hsa-19386及其靶基因等的表达，揭示CTCs远处转移的深层次分子机制，为控制乳腺癌远处转移提供靶向CTCs的新思路。

Circulating tumor cells (CTCs) are the key cell populations for distant metastasis of breast cancer. However, the specific mechanism of distant metastasis of breast cancer CTCs remains unclear. piRNAs have been shown to be key molecules in the regulation of tumor metastasis. The results of our previous studies found that: piR-hsa-19386 was reduced in CTCs, and its expression level was significantly negatively related to the number of CTCs, suggesting that piR-hsa-19386 was related to CTCs leaving the tumor nest; The over-expression of piR-hsa-19386 can inhibit the proliferation, invasion, tumor stemness, and epithelial-mesenchymal transition of CTCs of breast cancer, suggesting that piR-hsa-19386 participated in the distant metastasis of CTCs; piR-hsa-19386 can target the degenerative pseudogene MPRIPP1, releasing candidate miRNAs targeting MPRIP to regulate tumor metastasis. In order to further clarify the role and mechanism of piR-hsa-1986 in regulating the distant metastasis of CTCs in breast cancer, we intend to reveal the deep molecular mechanism of CTCs by intervening the expression of piR-hsa-1986 and its target genes in CTCs, in order to provide a new idea of targeting CTCs for controlling distant metastasis of breast cancer.