Song Yexun, Peng Xiaowei, Wang Min, Xie Jun, Tan Guolin
Department of Otolaryngology-Head Neck Surgery, The Third Xiangya Hospital of Central South University Changsha, Hunan, China.
Department of Head and Neck Surgery and Oncology Plastic Surgery, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University Changsha, Hunan, China.
Int J Clin Exp Pathol. 2015 Sep 1;8(9):11314-22. eCollection 2015.
Our previous study has shown that downregulation of FOLR1 by siRNA partially reversed taxol-resistant phenotype in taxol-resistant nasopharyngeal carcinoma cell lines. We aim to gain further insight into the molecular mechanisms of this process and identify the differentially expressed genes after FOLR1 downregulation.
The global gene expression profile was identified and analyzed using the Affymetrix HG-U133 Plus 2.0 array.
There was a significant dysregulation in the global gene expression of the FOLR1-suppressed taxol-resistant nasopharyngeal carcinoma cell lines. There were 41 upregulated genes and 109 downregulated genes. QRT-PCR validation of the selected differentially expressed genes demonstrated there was a good correlation with the microarray analysis. There was a significant deregulation of expression in the apoptosis-related genes such as BIRC3, PRKX, TNFRSF10A and involved in Viral carcinogenesis, MAPK signaling pathways after FOLR1 was downregulated.
The suppression of FOLR1 by RNA interference altered gene expression profile of taxol-resistant nasopharyngeal carcinoma cell lines. The apoptosis-related genes and the gene alterations in viral carcinogenesis, MAPK signaling pathways might be important in FOLR1 siRNA-induced taxol-resistant reversal.
我们之前的研究表明，通过小干扰RNA（siRNA）下调叶酸受体1（FOLR1）可部分逆转耐紫杉醇的鼻咽癌细胞系中的耐紫杉醇表型。我们旨在进一步深入了解这一过程的分子机制，并确定FOLR1下调后差异表达的基因。
使用Affymetrix HG-U133 Plus 2.0芯片鉴定并分析整体基因表达谱。
FOLR1抑制的耐紫杉醇鼻咽癌细胞系的整体基因表达存在显著失调。有41个基因上调，109个基因下调。对所选差异表达基因进行的实时定量聚合酶链反应（QRT-PCR）验证表明，与微阵列分析有良好的相关性。FOLR1下调后，凋亡相关基因如杆状病毒IAP重复序列3（BIRC3）、X染色体连锁的丝氨酸/苏氨酸蛋白激酶（PRKX）、肿瘤坏死因子受体超家族成员10A（TNFRSF10A）以及参与病毒致癌、丝裂原活化蛋白激酶（MAPK）信号通路的基因表达出现显著失调。
RNA干扰抑制FOLR1改变了耐紫杉醇鼻咽癌细胞系的基因表达谱。凋亡相关基因以及病毒致癌、MAPK信号通路中的基因改变可能在FOLR1 siRNA诱导的耐紫杉醇逆转中起重要作用。
