Increased expression of REV7 in small cell lung carcinomas and its association with tumor cell survival and proliferation
Increased expression of REV7 in small cell lung carcinomas and its association with tumor cell survival and proliferation
复制标题
DOI：
10.1111/pin.13040
复制
发表时间：
2020-10
影响因子：
2.2
通讯作者：
Itaru Sanoyama;Yasutaka Sakurai;M. Ichinoe;A. Hoshino;Yurika Kesen;Takuya Kato;Y. Numata;Atsuko Umezawa;Shi‐Xu Jiang;Y. Murakumo
中科院分区：
文献类型：
--
作者：
Itaru Sanoyama;Yasutaka Sakurai;M. Ichinoe;A. Hoshino;Yurika Kesen;Takuya Kato;Y. Numata;Atsuko Umezawa;Shi‐Xu Jiang;Y. Murakumo
REV 7参与多种生物学过程，包括DNA损伤耐受、细胞周期调控和基因表达，并且是易突变DNA聚合酶E1的辅助亚基。据报道，REV 7表达与几种人类癌症的不良预后相关。本研究旨在探讨REV 7在肺癌发生中的意义。手术切除的肺癌标本的免疫组织化学分析显示，REV 7显示出增加的表达在小细胞肺癌（SCLC）相比，其他组织学类型的肺癌。REV 7表达水平和临床病理因素之间的关联进行了研究，使用SCLC的情况下，或没有手术切除。我们的分析显示，高REV 7表达与肿瘤细胞增殖显著相关，通过Ki-67标记指数评估，与远处转移和广泛期疾病呈负相关。REV 7表达与其他因素（包括SCLC的预后或对放化疗的反应）之间没有显著相关性。使用SCLC细胞系证实了SCLC中REV 7表达的增加。此外，siRNA介导的REV 7耗竭激活了SCLC细胞中的凋亡途径并抑制了细胞生长。这些结果表明REV 7在SCLC中的肿瘤细胞存活和增殖中起重要作用。
REV7 is involved in multiple biological processes including DNA damage tolerance, cell cycle regulation and gene expression, and is an accessory subunit of the mutation‐prone DNA polymerase ζ. It has been reported that REV7 expression is associated with poor prognosis in several human cancers. The aim of this study is to investigate the significance of REV7 in lung carcinogenesis. Immunohistochemical analyses of surgically resected lung cancer specimens revealed that REV7 shows an increased expression in small cell lung carcinomas (SCLCs) when compared with other histological types of lung carcinoma. Association between REV7 expression levels and clinicopathological factors was investigated using SCLC cases with or without surgical resection. Our analyses revealed that high REV7 expression significantly correlated with tumor cell proliferation, assessed by Ki‐67 labeling indices, and was negatively associated with distant metastasis and extensive‐stage disease. No significant association was detected between REV7 expression and other factors, including prognosis or response to chemoradiotherapy in SCLC. Increase in REV7 expression in SCLC was confirmed using SCLC cell lines. In addition, siRNA‐mediated depletion of REV7 activated the apoptotic pathway and suppressed cell growth in SCLC cells. These results suggest that REV7 plays an important role in tumor cell survival and proliferation in SCLC.