Syntaxin 18 regulates the DNA damage response and epithelial-to-mesenchymal transition to promote radiation resistance of lung cancer

Radiotherapy is an important modality in lung cancer treatment. Despite advances in treatment planning and dose delivery, patient benefit is still limited by in-field relapse and metastatic recurrence. In an unbiased functional genetic screen for radiosensitization targets in lung cancer we identified syntaxin 18 (STX18), a protein involved in retrograde vesicular transport between the Golgi apparatus and endoplasmic reticulum, as mediator of radioresistance. In order to identify possible targets of STX18, we performed mRNA sequencing in A549 cells with and without shRNA-mediated knockdown of STX18 (A549 shSTX18 and A549 shScr, respectively), which were mock irradiated or irradiated with 10 Gy and analyzed after 24h.

放射治疗是肺癌临床治疗的重要手段。尽管治疗规划与剂量递送技术已有长足进步，但患者的临床获益仍受限于靶区复发与远处转移复发。本研究通过针对肺癌放射增敏靶点的无偏倚功能遗传筛选，鉴定出突触融合蛋白18（syntaxin 18, STX18）——一种参与高尔基体（Golgi apparatus）与内质网（endoplasmic reticulum）之间逆行囊泡运输过程的蛋白质——作为放射抵抗的介导因子。为鉴定STX18的潜在调控靶点，本研究对两组A549细胞开展mRNA测序：一组为经短发夹RNA（short hairpin RNA, shRNA）介导敲低STX18的A549 shSTX18细胞，另一组为阴性对照的A549 shScr细胞；两组细胞均分别接受假照射或10戈瑞（Gy）照射，并于照射后24小时完成测序分析。