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The disorders of polymerase theta (POLQ) were reported to contribute to GIN and progression in many cancers. Here, we found that POLQ over\u2010expression was related to salivary adenoid cystic carcinoma (SACC) progression and poor prognosis. Then, we investigated the role and mechanism of POLQ in the GIN in SACC. GIN was assessed by chromosome staining with DAPI and Giemsa, as well as qRT\u2010PCR of the mitosis\u2010related gene expression. Meanwhile, PCR\u2010SSCP was used to evaluate microsatellite instability. Modulation of POLQ expression increased chromosomal instability and enhanced the sensitivity to etoposide without impacting microsatellite stability. Mechanistically, POLQ regulated genome stability by promoting the expression of the error\u2010prone alt\u2010NHEJ\u2010related protein PARP1, and down\u2010regulating c\u2010NHEJ\u2010 and HR\u2010related proteins KU70 and RAD51. In vitro CCK, Transwell assays and in vivo murine xenograft models indicated that the PARP inhibitor olaparib suppressed SACC growth in the case of etoposide\u2010induced DNA damage. Bioinformatic analysis identified CEBPB as a potential POLQ\u2010regulating transcription factor. In summary, our research provides new insights into the mechanisms of SACC chromosomal instability and identifies new potential targets for SACC treatment.<\/jats:p>","DOI":"10.1111\/jcmm.17429","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T09:51:59Z","timestamp":1655805119000},"page":"3931-3949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Altered polymerase theta expression promotes chromosomal instability in salivary adenoid cystic carcinoma"],"prefix":"10.1111","volume":"26","author":[{"given":"Han","family":"Bai","sequence":"first","affiliation":[{"name":"College of Stomatology Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Xia","sequence":"additional","affiliation":[{"name":"Clinical Laboratory of Integrative Medicine The First Affiliated Hospital of Dalian Medical University  Dalian 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