微创医学

目的探究周期蛋白依赖性激酶2相互作用蛋白（CINP）在肺腺癌中的表达情况及其对肺腺癌增殖、迁移、侵袭力的影响。方法利用生物信息学分析CINP在基因表达综合数据库（GEO）的不同数据集中的表达和预后情况。收集15例原发性肺腺癌患者的癌组织和癌旁组织进行实时荧光定量PCR实验验证CINP在肺腺癌组织中的表达情况。利用人肺腺癌细胞A549和NCI-H1299构建敲低CINP的细胞系，进行5-乙炔基-2’-脱氧尿嘧啶细胞增殖（EdU）实验、Transwell实验和划痕实验探究CINP基因表达与肺腺癌进展的相关性。结果在GSE10072、GSE30219数据集中，CINP基因在肺腺癌组织的表达水平均高于正常肺组织，差异有统计学意义（P<0.05）。根据GSE30219数据集肺腺癌患者的CINP mRNA表达情况将患者分为CINP低表达组和CINP高表达组。与CINP低表达组患者相比，CINP高表达组患者的生存时间和复发时间均更短，差异均有统计学意义（均P<0.05）。对15例肺腺癌患者的肺腺癌组织和癌旁组织CINP mRNA表达水平检测结果显示，肺腺癌组织的CINP mRNA相对表达水平显著高于癌旁组织，差异有统计学意义（P<0.05）。采用siRNA构建敲低CINP的A549和H1299肺腺癌细胞系。结果显示，敲低CINP后，两个细胞系CINP mRNA相对表达水平均显著降低（均P<0.05）。与阴性对照组（si-NC）相比，在转染48 h后，两个细胞系si-CINP组的EdU阳性率均显著降低（均P<0.05）。与si-NC组相比，敲低CINP后，两个细胞系的细胞迁移和侵袭能力均显著降低（均P<0.05）。与si-NC组相比，si-CINP组24 h、48 h细胞划痕面积愈合率均显著降低（均P<0.05）。结论 CINP在肺腺癌组织中呈高表达状态，且与肺腺癌患者的不良预后有关，敲低CINP可以抑制肺腺癌细胞的增殖、迁移和侵袭能力。

Objective To investigate the expression of cyclin-dependent kinase 2-interacting protein (CINP) in lung adenocarcinoma and its effect on proliferation, migration and invasion of lung adenocarcinoma. Methods Bioinformatics analysis was conducted to examine the expression and prognosis of CINP in various datasets from the Gene Expression Omnibus (GEO) database. The expression levels of CINP in lung adenocarcinoma tissues and adjacent tissues from 15 patients with primary lung adenocarcinoma were validated using real-time fluorescence quantitative PCR. Cell lines with knocked-down CINP were established using human lung adenocarcinoma cells A549 and NCI-H1299, and 5-Ethynyl-2'-deoxyuridine cell proliferation (EdU) assays, Transwell assays, and wound healing assays were performed to explore the correlation between CINP gene expression and the progression of lung adenocarcinoma. Results In the GSE10072 and GSE30219 datasets, the expression level of the CINP gene in lung adenocarcinoma tissues was significantly higher than that in normal lung tissues, with statistically significant differences (P<0.05). According to the CINP mRNA expression of lung adenocarcinoma patients in GSE30219 dataset, these patients were classified into a CINP low-expression group and a CINP high-expression group. CINP high-expression group had shorter survival and recurrence times compared to those with CINP low-expression group (all P<0.05). The dectection results of the CINP mRNA expression levels in both the lung adenocarcinoma tissues and the adjacent tissues of 15 lung adenocarcinoma patients revealed that the relative expression level of CINP mRNA in the lung adenocarcinoma tissues was notably higher than that in the adjacent tissues, and this difference was statistically significant (P<0.05). The siRNA was applied to engineer A549 and H1299 lung adenocarcinoma cell lines with knocked-down CINP expression. The results demonstrated that following the knocked-down of CINP, the relative expression levels of CINP mRNA in both cell lines were markedly reduced (all P<0.05). Compared to the si-NC group, at 48 hours after transfection, the si-CINP group in two cell lines showed a significant decrease in the EdU positive rate (all P<0.05), while after CINP knockdown, these cell lines also presented significantly reduced cell migration and invasion abilities (all P<0.05), and at 24 and 48 hours, the si-CINP group had a significantly lower healing rate of the cell scratch area compared to the si-NC group (all P<0.05). Conclusion CINP is over-expressed in lung adenocarcinoma tissues and is associated with poor prognosis in lung adenocarcinoma patients. Moreover, the knockdown of CINP can inhibit the proliferation, migration, and invasion capabilities of lung adenocarcinoma cells.

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