Journal
IMMUNOLOGIC RESEARCH
Volume 69, Issue 6, Pages 558-567Publisher
HUMANA PRESS INC
DOI: 10.1007/s12026-021-09237-w
Keywords
Breast cancer; circ_0001598; miR-1184; PD-L1; Trastuzumab-resistance
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In breast cancer, circ_0001598 might play a crucial role, particularly in cases of trastuzumab resistance. MiR-1184 and PD-L1 are also involved in the regulation of BC progression and trastuzumab resistance, indicating that circ_0001598 could be a potential molecular target for treating HER2-positive BC patients.
Approximately 25% of breast cancer (BC) patients are HER2-positive. Trastuzumab is used as a targeted therapy drug to treat HER2-positive BC patients; however, the drug resistance remains a big challenge. Circular RNAs (circRNAs) are reported to be involved in drug resistance, but the role of circ_0001598 has never been studied in BC. First, we identified the expression of circ_0001598 by RT-qPCR in BC. The gain-of-function and loss-of-function studies were applied to study the functional roles of circ_0001598 and its target gene. We observed upregulation of circ_0001598 in BC tissues, especially in trastuzumab-resistant BC samples. We further identified that miR-1184 is a functional target of circ_0001598. Moreover, it was found that programmed death-ligand 1 (PD-L1) was a direct target of miR-1184. The oncogenic effects of circ_0001598 in promoting BC cell growth, trastuzumab-resistance, PD-L1 expression, and escaping of CD8 T cell killing were abolished after the restoration of miR-1184. In conclusion, we demonstrate that circ_0001598/miR-1184/PD-L1 signaling plays a crucial role in the regulation of BC progression and trastuzumab-resistance phonotypes, which suggests that circ_0001598 may be a molecular target to treat HER2-positive BC patients.
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