Department of Medical Oncology, The First Affiliated Hospital, University of South China, Hengyang 421001, Hunan Province, China.
Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang 421001, Hunan Province, China.
Aging (Albany NY). 2020 Aug 3;12(15):15532-15545. doi: 10.18632/aging.103746.
As a unique type of RNA, circular RNAs (circRNAs) are important regulators of multiple biological processes in the progression of cancer. However, the potential role of most circRNAs in breast cancer lung metastasis is still unknown. In this study, we characterized and further investigated circIQCH (hsa_circ_0104345) by analyzing the circRNA microarray profiling in our previous study. circIQCH was upregulated in breast cancer tissues, especially in the metastatic sites. CCK-8, transwell, wound-healing and mouse xenograft assays were carried out to investigate the functions of circIQCH. Knockdown of circIQCH inhibited breast cancer cell proliferation and migration to lung. Moreover, luciferase reporter assays and RNA immunoprecipitation assays were performed to elucidate the underlying molecular mechanism of circIQCH. The results showed that circIQCH sponges miR-145 and promotes breast cancer progression by upregulating DNMT3A. In summary, our study demonstrated the pivotal role of circIQCH-miR-145-DNMT3A axis in breast cancer growth and metastasis via the mechanism of competing endogenous RNAs. Thus, circIQCH could be a potential therapeutic target for breast cancer.
作为一种独特类型的 RNA，环状 RNA（circRNAs）是癌症进展中多种生物过程的重要调节剂。然而，大多数 circRNAs 在乳腺癌肺转移中的潜在作用仍不清楚。在这项研究中，我们通过分析我们之前研究中的 circRNA 微阵列分析，对 circIQCH（hsa_circ_0104345）进行了表征和进一步研究。circIQCH 在乳腺癌组织中上调，特别是在转移部位。CCK-8、Transwell、划痕愈合和小鼠异种移植实验用于研究 circIQCH 的功能。circIQCH 的敲低抑制了乳腺癌细胞向肺的增殖和迁移。此外，进行了荧光素酶报告基因检测和 RNA 免疫沉淀实验以阐明 circIQCH 的潜在分子机制。结果表明，circIQCH 海绵 miR-145 并通过上调 DNMT3A 促进乳腺癌进展。总之，我们的研究通过竞争内源性 RNA 的机制证明了 circIQCH-miR-145-DNMT3A 轴在乳腺癌生长和转移中的关键作用。因此，circIQCH 可能是乳腺癌的潜在治疗靶点。
