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Although PARP inhibitor (PARPi) offers great promise in treating TNBC with deficiency in homologous recombination (HR), most TNBC patients are HR-proficient. Furthermore, acquired resistance to PARPi remains as a challenge. Thus, there is an unmet need to identify new therapeutic target for developing advanced TNBC treatment strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      I-SceI reporter assay and alkaline comet assay were used to analyze the role of\n                      <jats:italic>Smyca<\/jats:italic>\n                      in HR repair. Ingenuity pathway analysis was used to identify upstream regulators of\n                      <jats:italic>Smyca<\/jats:italic>\n                      -regulated transcriptome. RNA immunoprecipitation and RNA pull down were used to examine\n                      <jats:italic>Smyca<\/jats:italic>\n                      -FOXM1 interaction. Chromatin immunoprecipitation followed by sequencing was performed to identify FOXM1 target genes that are regulated by\n                      <jats:italic>Smyca<\/jats:italic>\n                      . Chromatin isolation by RNA purification was used to determine\n                      <jats:italic>Smyca<\/jats:italic>\n                      loading onto the promoters of FOXM1 target genes. Patient-derived organoid and xenograft mouse models were performed to evaluate the effect of\n                      <jats:italic>Smyca<\/jats:italic>\n                      on chemoresistance. Nanoparticle-assisted gapmer antisense oligonucleotides delivery was used to target\n                      <jats:italic>Smyca<\/jats:italic>\n                      in vivo. Co-culture of CD3\u2009+\u2009T cells with TNBC cells and syngeneic mouse model were used to examine the effect of\n                      <jats:italic>Smyca<\/jats:italic>\n                      -FOXM1 targeting on anti-tumor immunity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The long non-coding RNA\n                      <jats:italic>Smyca<\/jats:italic>\n                      is highly expressed in TNBC. We show that\n                      <jats:italic>Smyca<\/jats:italic>\n                      is induced by genotoxic agents to enhance HR repair. Mechanistically,\n                      <jats:italic>Smyca<\/jats:italic>\n                      binds FOXM1 and promotes the recruitment of FOXM1 to the promoters of a set of HR and nucleotide metabolism genes, thereby promoting their expression.\n                      <jats:italic>Smyca<\/jats:italic>\n                      ablation induces BRCAness in HR-proficient TNBC, thereby sensitizing these tumors to platinum or PARPi. Furthermore, targeting\n                      <jats:italic>Smyca<\/jats:italic>\n                      -FOXM1 complex in combination with platinum or PARPi activates cGAS\/STING pathway and tumor immunogenicity to enhance anti-tumor immune surveillance. Clinically,\n                      <jats:italic>Smyca<\/jats:italic>\n                      expression in breast cancer patients correlates positively with therapy resistance and negatively with HR deficiency, interferon signature, and infiltration of anti-tumor immune cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study identifies an unprecedented role of\n                      <jats:italic>Smyca<\/jats:italic>\n                      in HR repair to promote TNBC survival and immune evasion in response to therapy and suggests\n                      <jats:italic>Smyca<\/jats:italic>\n                      as a potential target for sensitizing TNBC to chemotherapy, PARPi, or immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12929-026-01279-2","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T02:50:19Z","timestamp":1786416619000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Smyca-FOXM1 ribonucleoprotein complex promotes homologous recombination and tumor immune evasion to define a therapeutic target of triple-negative breast cancer"],"prefix":"10.1186","volume":"33","author":[{"given":"Han-Hsiun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keng-Hao","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin-Rong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hao","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Yu","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tera","family":"Carissa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Duo","family":"Hsu Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Ling","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily Hui-Ching","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che-Ming","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3810-4860","authenticated-orcid":false,"given":"Hsin-Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruey-Hwa","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"issue":"11","key":"1279_CR1","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/nrclinonc.2016.66","volume":"13","author":"G Bianchini","year":"2016","unstructured":"Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. 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