The lncRNA DANCR promotes breast cancer brain metastasis by acting as a ceRNA for miR-758-3p to regulate PTGS2 expressionOA
Brain metastases in breast cancer patients are correlated with markedly lower survival rates than extracranial metastases,highlighting the critical necessity for identifying novel therapeutic targets.The functional involvement of differentiation antagonizing nonprotein coding RNA(DANCR)in the pathogenesis of breast cancer brain metastases(BCBMs)has yet to be fully elucidated.Bioinformatics analyses identify DANCR as a potential specific prognostic biomarker of BCBM.CCK-8,transwell,and wound healing assays are performed to examine the effects of DANCR on the proliferation,migration,and invasion of tumors,along with in vivo assays.Mechanistic insights are obtained through quantitative real-time polymerase chain reaction(qRT-PCR),western blot analysis,and dual-luciferase reporter assays.DANCR is markedly upregulated in BCBM and specifically correlates with the prognostic risk of BCBM.DANCR overexpression significantly enhances breast cancer cell proliferation,migration,and invasion.According to low-throughput screening,only the expression of prostaglandin-endoperoxide synthase 2(PTGS2)consistently varies in parallel with that of DANCR,and PTGS2 silencing reverses DANCR-induced protumor effects in vitro.Additionally,in brain metastatic lesions,PTGS2 expression is also elevated in patients with increased DANCR expression.Mechanistically,DANCR and PTGS2 possess a conserved miR-758-3p response element.DANCR directly binds to and sequesters miR-758-3p,thereby alleviating the suppressive effects of miR-758-3p on both DANCR and PTGS2.When the miR-758-3p binding site on DANCR is mutated,this interaction is completely abolished.DANCR drives BCBM by functioning as a miR-758-3p sponge to upregulate PTGS2.Targeting the DANCR/miR-758-3p/PTGS2 axis represents a promising therapeutic approach.
Sen Li;Yuechao Yang;Zhisu Wang;Liangdong Li;Yang Gao;Yiqun Cao
Department of Neurosurgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,ChinaDepartment of Neurosurgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,ChinaDepartment of Neurosurgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,ChinaDepartment of Neurosurgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,ChinaDepartment of Neurosurgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,ChinaDepartment of Neurosurgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China
医药卫生
DANCRbreast cancerbrain metastasisPTGS2
《Acta Biochimica et Biophysica Sinica》 2026 (3)
P.610-620,11
supported by the grants from the National Natural Science Foundation of China(Nos.82173177,82472955,82103429)the Foundation of Shanghai Anticancer Association EYAS PROJECT(No.SACA-CY22B08)the Beijing Xisike Clinical Oncology Research Foundation(No.Y-Young2024-0374).
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