核不均一核糖核蛋白R基因沉默抑制非小细胞肺癌细胞恶性转化

核不均一核糖核蛋白R(hnRNPR)是一种与mRNA生物学功能密切相关的RNA结合蛋白质,与多种肿瘤细胞的恶性转化相关。然而,在非小细胞肺癌(NSCLC)中的作用机制尚不清楚。本研究通过检索公共数据库发现,hnRNPR蛋白主要在肺癌细胞核中表达,hnRNPR mRNA在非小细胞肺癌组织中高表达,并且与肺腺癌患者的生存率呈负相关;hnRNPR的表达与非小细胞肺癌患者的性别、T分期显著相关(P<0.05)。构建hnRNPR基因沉默的非小细胞肺癌稳定细胞株,检测细胞功能变化,结果显示,hnRNPR基因沉默抑制了细胞增殖、迁移和侵袭能力以及上皮-间质转化(EMT),并将细胞周期阻滞在G₁期(P＜0.01)。生物信息学分析显示,非小细胞肺癌中hnRNPR基因与9 310个基因的表达正相关(皮尔逊相关系数>0,P<0.05),与10 680个基因的表达负相关(皮尔逊相关系数<0,P<0.05)。综上所述,hnRNPR在非小细胞肺癌中高表达,可能作为剪接体的组分,通过调节相关基因的表达,促进了NSCLC细胞的恶性转化。

Heterogeneous Nuclear Ribonucleoprotein R (hnRNPR) Gene Silencing Inhibits the Malignant Transformation of Non-small-cell Lung Cancer Cells

Heterogeneous nuclear ribonucleoprotein R (hnRNPR) is an RNA-binding protein closely related to the biological function of mRNA, which is involved in the malignant transformation of various tumor cells. However, the role and mechanism of hnRNPR in non-small-cell lung cancer (NSCLC) are still unclear. In this study, the database analysis shows that hnRNPR is mainly expressed in the nucleus of lung cancer cells. Moreover, compared with the normal lung tissues, the mRNA expression of hnRNPR was higher in NSCLC tissues, which was negatively correlated with the survival rate of lung adenocarcinoma (LUAD) patients and significantly related to the gender and T stage of NSCLC patients (P<0.05). Two stable NSCLC cell lines with the hnRNPR gene silenced were constructed. Then cell function assays have indicated that hnRNPR silencing inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) and arrested the cell cycle at the G₁ phase (P<0.01). The bioinformatics analysis has shown that the mRNA expression of hnRNPR in NSCLC was positively correlated with the expressions of 9 310 genes (Pearson correlation coefficient>0, P<0.05), and negatively with 10 680 genes (Pearson correlation coefficient<0, P<0.05). In conclusion, the expression of hnRNPR is upregulated in NSCLC, which may promote the malignant transformation of NSCLC cells by regulating the expression of related genes as a component of spliceosome.