biostudies-literatureYi JMinistry of Science and Technology of the People's Republic of China (MOST)MOST | National Natural Science Foundation of China (NSFC)e2420383122https://www.ebi.ac.uk/biostudies/studies/S-EPMC11874584biostudies-literatureUnknown122(8)The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and drug resistance remain incompletely understood. Elevated expression of CCND1 is linked to enhanced invasiveness, poorer prognosis, and resistance to drug therapies in ER-positive breast cancer. In this study, we identify a highly expressed circular RNA (circRNA) derived from <i>FOXK2</i>, called circFOXK2, which plays a key role in stabilizing <i>CCND1</i> mRNA, thereby promoting cell cycle progression, cell growth, and endocrine therapy resistance in ER-positive breast cancer cells. Mechanistically, circFOXK2 binds directly to <i>CCND1</i> mRNA via RNA-RNA pairing and recruits the RNA-binding protein ELAVL1/HuR, stabilizing the <i>CCND1</i> mRNA and enhancing CCND1 protein levels. This results inProceedings of the National Academy of Sciences of the United States of AmericaA circRNA-mRNA pairing mechanism regulates tumor growth and endocrine therapy resistance in ER-positive breast cancer.PMC11874584U22A20320822732362020YFA08036002023YFA0915602821250282020YFA01123003187131991953114Yi JZhang YYHu GSNie RCHe HLuo DXDu JChen XChen SWen XSWang LLiu WfalseA circRNA-mRNA pairing mechanism regulates tumor growth and endocrine therapy resistance in ER-positive breast cancer.The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and drug resistance remain incompletely understood. Elevated expression of CCND1 is linked to enhanced invasiveness, poorer prognosis, and resistance to drug therapies in ER-positive breast cancer. In this study, we identify a highly expressed circular RNA (circRNA) derived from <i>FOXK2</i>, called circFOXK2, which plays a key role in stabilizing <i>CCND1</i> mRNA, thereby promoting cell cycle progression, cell growth, and endocrine therapy resistance in ER-positive breast cancer cells. Mechanistically, circFOXK2 binds directly to <i>CCND1</i> mRNA via RNA-RNA pairing and recruits the RNA-binding protein ELAVL1/HuR, stabilizing the <i>CCND1</i> mRNA and enhancing CCND1 protein levels. This results in2025-01-01T00:00:00Z2025 Feb2025-07-10T03:08:21.818Z2025-07-10T03:08:21.818ZS-EPMC118745844023341010.1073/pnas.2420383122