Zhu Xiaozhong, Zou Shitao, Zhou Jundong, Zhu Hongsheng, Zhang Shuyu, Shang Zengfu, Ding Wei-Qun, Wu Jinchang, Chen Yihong
Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001, P.R. China.
Suzhou Cancer Center Core Laboratory, Suzhou, Jiangsu 215001, P.R. China.
Oncol Rep. 2016 Mar;35(3):1664-70. doi: 10.3892/or.2016.4549. Epub 2016 Jan 5.
Protein reversionless 3-like (REV3L), the catalytic subunit of DNA polymerase (pol) ζ, is well known to participate in error-prone translesion synthesis (TLS) with less stringent and lower processivity. Recent evidence has demonstrated that REV3L is involved in carcinogenesis and tumor progression. However, the function of REV3L remains unclear in esophageal squamous cell carcinoma (ESCC). In the present study, we examined REV3L expression in ESCC tissues and its association with clinicopathological parameters. REV3L was found to be significantly upregulated and correlated with lymph node metastasis and clinical stage in the ESCC tissues. To further investigate the potential role of REV3L in esophageal cancer, stable ESCC cell lines with suppression of REV3L expression were established. Downregulation of REV3L expression led to a decrease in cell proliferation and invasive capacity partly through suppression of cyclin D1 and survivin expression, and an increase in cellular sensitivity to 5-fluorouracil (5-FU) by induction of G1 phase arrest and apoptosis. Therefore, REV3L plays an important role in ESCC progression and chemoresistance, and is a potential diagnostic marker and therapeutic target for ESCC.
蛋白质无回复3样蛋白（REV3L）是DNA聚合酶（pol）ζ的催化亚基，众所周知，它参与易错跨损伤合成（TLS），具有较低的严格性和较低的持续合成能力。最近的证据表明，REV3L参与致癌作用和肿瘤进展。然而，REV3L在食管鳞状细胞癌（ESCC）中的功能仍不清楚。在本研究中，我们检测了REV3L在ESCC组织中的表达及其与临床病理参数的关系。发现REV3L在ESCC组织中显著上调，且与淋巴结转移和临床分期相关。为了进一步研究REV3L在食管癌中的潜在作用，建立了REV3L表达受抑制的稳定ESCC细胞系。REV3L表达下调部分通过抑制细胞周期蛋白D1和生存素的表达导致细胞增殖和侵袭能力下降，并通过诱导G1期阻滞和凋亡增加细胞对5-氟尿嘧啶（5-FU）的敏感性。因此，REV3L在ESCC进展和化疗耐药中起重要作用，是ESCC潜在的诊断标志物和治疗靶点。
