Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, 1055 San Xiang Road, Suzhou, Jiangsu 215004, China; Institute of Radiotherapy and Oncology, Soochow University, Suzhou, Jiangsu 215004, China; Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan Road, Nanjing, Jiangsu 210011, China.
Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan Road, Nanjing, Jiangsu 210011, China.
Gene. 2021 Mar 10;772:145358. doi: 10.1016/j.gene.2020.145358. Epub 2020 Dec 17.
FAM135B (family with sequence similarity 135, member B) is related to the progression of esophageal squamous cell carcinoma (ESCC). However, the role played by the gene in radiosensitivity remains unknown. Herein, we examined the relationship between FAM135B and radiosensitivity. According to the results, FAM135B is highly expressed in ESCC cells, and ESCC cells with high levels of FAM135B are resistant to irradiation. Silencing FAM135B inhibits colony formation capability and cell cycle protein expression (pP53, CDK1), promotes cell cycle arrest at the G2/M phase following irradiation. Moreover, transcriptome sequencing analysis demonstrates that FAM135B regulates downstream PI3K/Akt/mTOR signaling pathway, and western blot verifies the result. One of the mechanisms of increasing radiosensitivity by silencing FAM135B expression in ESCC cells may be achieved by regulating the PI3K/Akt/mTOR signaling pathway. Silencing FAM135B shows synergy with PI3K/Akt/mTOR pathway inhibitor (rapamycin) in increasing radiosensitivity, regulating the expression of cell cycle protein and inducing apoptosis of ESCC cells. The results indicate that FAM135B could be a potential treatment target for ESCC in management of radiosensitivity.
FAM135B（家族与序列相似性 135，成员 B）与食管鳞状细胞癌（ESCC）的进展有关。然而，该基因在放射敏感性中的作用尚不清楚。在此，我们研究了 FAM135B 与放射敏感性之间的关系。结果表明，FAM135B 在 ESCC 细胞中高表达，高水平的 FAM135B 的 ESCC 细胞对辐射具有抗性。沉默 FAM135B 抑制集落形成能力和细胞周期蛋白表达（pP53、CDK1），并在照射后促进细胞周期停滞在 G2/M 期。此外，转录组测序分析表明 FAM135B 调节下游的 PI3K/Akt/mTOR 信号通路，Western blot 验证了这一结果。沉默 FAM135B 表达可通过调节 PI3K/Akt/mTOR 信号通路来增加 ESCC 细胞的放射敏感性。沉默 FAM135B 与 PI3K/Akt/mTOR 通路抑制剂（雷帕霉素）联合使用可增加放射敏感性，调节细胞周期蛋白的表达并诱导 ESCC 细胞凋亡。结果表明，FAM135B 可能是 ESCC 管理放射敏感性的潜在治疗靶标。
