RAC2 promotes abnormal proliferation of quiescent cells by enhanced JUNB expression via the MAL-SRF pathway
RAC2 promotes abnormal proliferation of quiescent cells by enhanced JUNB expression via the MAL-SRF pathway
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RAC2通过MAL-SRF途径增强JUNB表达促进静止细胞异常增殖
DOI：
10.1080/15384101.2018.1480217
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发表时间：
2018-01-01
期刊：
影响因子：
4.3
通讯作者：
Zhou, Guangming
中科院分区：
文献类型：
--
作者：
Pei, Hailong;Guo, Ziyang;Zhou, Guangming
摘要 放射性肺损伤（RILI）最常发生在肺癌、食管癌和其他胸部癌症的放射治疗中。 RILI的发生是一个复杂的过程，包括多种细胞和分子相互作用，最终导致癌变。然而，根本机制尚不清楚。在这里，我们发现 Ras 相关的 C3 肉毒毒素底物 2 (RAC2) 和转录因子 jun-B (JUNB) 在非小细胞癌 (NSCLC) 组织中表达上调，并且与 NSCLC 患者的不良预后相关。电离辐射还导致静止期细胞中 RAC2 表达增加，并使静止期细胞重新进入新的细胞周期。血清反应因子 (SRF) 的活性由 RAC2 和其他 Rho 家族基因（RhoA、ROCK 和 LIM 激酶）激活。因此，JUNB 作为癌基因并诱导静止细胞的异常增殖。总之，结果表明RAC2可以作为辐射防护的靶基因。更好地了解肺癌分子病因学中的 RAC2 和 JUNB 机制将有助于降低治疗该疾病期间的癌症风险和副作用。因此，我们的研究为 RAC2 和 JUNB 作为癌基因参与 NSCLC 肿瘤发生提供了新的视角。
ABSTRACT Radiation-induced lung injury (RILI) occurs most often in radiotherapy of lung cancer, esophageal cancer, and other thoracic cancers. The occurrence of RILI is a complex process that includes a variety of cellular and molecular interactions, which ultimately result in carcinogenesis. However, the underlying mechanism is unknown. Here we show that Ras-related C3 botulinum toxin substrate 2 (RAC2) and transcription factor jun-B (JUNB) were upregulated in non-small cell carcinoma (NSCLC) tissues and were associated with poor prognoses for NSCLC patients. Ionizing radiation also caused increased expression of RAC2 in quiescent stage cells, and the reentry of quiescent cells into a new cell cycle. The activity of the serum response factor (SRF) was activated by RAC2 and other Rho family genes (RhoA, ROCK, and LIM kinase). Consequently, JUNB acted as an oncogene and induced abnormal proliferation of quiescent cells. Together, the results showed that RAC2 can be used as a target gene for radiation protection. A better understanding of the RAC2 and JUNB mechanisms in the molecular etiology of lung cancer will be helpful in reducing cancer risks and side effects during treatment of this disorder. Our study therefore provides a new perspective on the involvement of RAC2 and JUNB as oncogenes in the tumorigenesis of NSCLC.