S1 RNA结合域1的沉默抑制人非小细胞肺癌细胞生长并促进细胞凋亡

2019年1月，北京协和医学院国家肿瘤中心/国家肿瘤临床研究中心/中国医学科学院肿瘤医院放射肿瘤科；北京环兴肿瘤医院放射肿瘤科(Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 10021, China；Department of Radiation Oncology, Cancer Hospital of Huan Xing, Beijing10021, China) Tao Zhang老师研究团队在《Translational lung cancer research》上发表论文：

“Silence of S1 RNA binding domain 1 represses cell growth and promotes apoptosis in human non-small cell lung cancer cells”

“S1 RNA结合域1的沉默抑制人非小细胞肺癌细胞生长并促进细胞凋亡”

Abstract：

Background: To investigate the expression of S1 RNA binding domain 1 (SRBD1) in non-small cell lung cancer tissue and the effects of SRBD1 silencing on the biological behaviors of human non-small cell lung cancer cells, and to explore the molecular mechanism of SRBD1functions in human non-small cell lung cancer cells.

Methods: Expressions of SRBD1 in human non-small cell lung cancer tissues and cell lines were examined by immunostaining and RT-PCR. shRNAs of SRBD1 were chemically synthesized and transfected into A549 and NCI-H1299 cells by lentivirus. Cell proliferation was assayed by cell counting, MTT and clone formation. Cell apoptosis was assayed by flow cytometry. Tumorigenicity was assessed by cell injection into BALB/c athymic nude mouse. Gene chip analysis was employed to explore genomic changes in A549 cells. Potential classical signaling pathways, upstream regulators and gene interaction networks were analyzed by Ingenuity Pathway Analysis, and verified by western blot analysis.

Results: SRBD1 was specifically expressed in human squamous cell carcinoma and highly expressed in lung cancer cell lines, NCI-H1299, A549 and NCI-H1975. SRBD1 directed-shRNA (shSRBD1) effectively reduced the expression of SRBD1 in A549 and NCI-H1299 cells. SRBD1 silencing inhibited cell proliferation, and promoted cell apoptosis in non-small cell lung cancer cells, and suppressed tumorigenesis in a nude mouse model. In addition, we found silencing of SRBD1 expression resulted in marked changes in gene expression in A549 cells. Besides, in shSRBD1 group, the protein levels of EPS 15, IGF1R, MYC, PYCR1 and HNRNPA0 were downregulated, and the expressions of several classical factors involved in the growth and apoptosis of cancer cells were also decreased.

Conclusions: We found that SRBD1 were specifically expressed in non-small cell lung cancer tissue. Silencing of SRBD1 inhibits cell growth and promotes cell apoptosis in non-small cell lung cancer cells, and suppresses tumorigenesis in vivo, suggesting that SRBD1 may be a new diagnostic indicator and therapeutic target of non-small cell lung cancer.

摘要：

背景:研究S1 RNA结合域1 (SRBD1)在非小细胞肺癌组织中的表达及SRBD1沉默对人非小细胞肺癌细胞生物学行为的影响，探讨SRBD1功能在人非小细胞肺癌细胞中的分子机制。

方法:采用免疫染色法和RT-PCR检测SRBD1在人非小细胞肺癌组织和细胞系中的表达。化学合成SRBD1的shrna，用慢病毒转染A549和NCI-H1299细胞。通过细胞计数、MTT和克隆形成检测细胞增殖。流式细胞术检测细胞凋亡。通过细胞注射BALB/c胸腺裸鼠评价细胞的致瘤性。采用基因芯片分析A549细胞的基因组变化。采用Ingenuity Pathway Analysis分析潜在的经典信号通路、上游调控因子和基因相互作用网络，并采用western blot分析进行验证。

结果:SRBD1在人鳞状细胞癌中特异表达，在肺癌细胞系NCI-H1299、A549和NCI-H1975中高表达。SRBD1定向shrna (shSRBD1)可有效降低A549和NCI-H1299细胞中SRBD1的表达。在裸鼠模型中，SRBD1沉默抑制非小细胞肺癌细胞增殖，促进细胞凋亡，抑制肿瘤发生。此外，研究人员发现沉默SRBD1表达可导致A549细胞中基因表达的显著变化。此外，shSRBD1组EPS 15、IGF1R、MYC、PYCR1和HNRNPA0蛋白水平下调，参与癌细胞生长和凋亡的几个经典因子的表达也下降。

结论:研究人员发现SRBD1在非小细胞肺癌组织中特异性表达。沉默SRBD1可抑制非小细胞肺癌细胞生长，促进细胞凋亡，抑制体内肿瘤发生，提示SRBD1可能成为非小细胞肺癌新的诊断指标和治疗靶点。

该论文中，人肺癌细胞系A549、NCI-H1299、NCI-H1975和95-D体外培养是使用Ausbian特级胎牛血清完成的。欲了解或购买Ausbian特级胎牛血清可以联系北京缔一生物400-166-8600.