CHD5 is a potential tumor suppressor in non small cell lung cancer (NSCLC)

CHD5 is a potential tumor suppressor in non small cell lung cancer (NSCLC)
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DOI:
10.1016/j.gene.2017.04.010
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发表时间:
2017-06-30
期刊:
影响因子:
3.5
通讯作者:
Buyru, Nur
Buyru, Nur
中科院分区:
生物学3区
文献类型:
--
作者:
Baykara, Onur;Tansarikaya, Merve;Buyru, Nur

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肺癌是最致命的癌症类型之一,遗传和表观遗传改变在其发展中起着重要作用。染色体结构域(CHD)蛋白家族在染色质组织、转录调控、基因组稳定性和癌症预防中起作用。虽然CHD 5,这个家族的一个成员,被证明有助于主要的细胞事件和功能作为一个肿瘤抑制基因在各种类型的癌症,目前还不清楚CHD 5是否在肺癌的发生中发挥作用。本研究的目的是探讨CHD 5在非小细胞肺癌(NSCLC)进展中的可能作用。采用qRT-PCR检测59例肺癌组织及相应非癌肺组织中CHD 5基因的表达水平,采用甲基化特异性PCR(methylation specific PCR,MS-PCR)检测CHD 5基因启动子区甲基化状态。Western Blot(WB)检测Akt磷酸化水平。CHD 5在17例(39.5%)肿瘤标本中表达下调,在24例(55.8%)肿瘤标本中表达上调。尽管在8例患者中CHD 5启动子高甲基化,但未发现与CHD 5基因表达相关(p = 0.08)。Akt磷酸化在14例(53.8%)样本中增加,在12例(46.2%)样本中减少,但在p-Akt磷酸化和CHD 5表达之间未发现显著相关性(p = 0.67)。我们认为,CHD 5可能作为一个抑癌基因在非小细胞肺癌。
Lung cancer is one of the deadliest types of cancers and genetic and epigenetic alterations play major roles in its development. Chromodomain (CHD) protein family acts in chromatin organization, regulation of transcription and also genomic stability and cancer prevention. Although CHD5, a member of this family was shown to contribute to major cellular events and functions as a tumor suppressor gene in various types of cancer, it is not clear whether CHD5 plays a role in lung carcinogenesis. The aim of this study was to investigate the possible role of CHD5 in progression of non-small cell lung cancer (NSCLC). Expression levels of CHD5 gene in 59 tumor and corresponding non-cancerous lung tissue samples were analyzed by qRT-PCR and the methylation status of the promoter region was investigated by methylation specific PCR (MS-PCR). The Akt phosphorylation levels were investigated by Western Blot (WB). CHD5 was down-regulated in 17 (39.5%) and up-regulated in 24 (55.8%) of tumor specimens. Even though the promoter of CHD5 was hypermethylated in 8 patients, it was not found associated with CHD5 gene expression (p = 0.08). Akt phosphorylation was increased in 14 (53.8%) and decreased in 12 (46.2%) of the samples but no significant association was found between p-Akt phosphorylation and CHD5 expression (p = 0.67). We suggest that CHD5 may act as a tumor suppressor gene in NSCLC.