基于多组学整合的前列腺癌同源框基因NKX3.1调控相关基因研究

A multi-omics study on NKX3.1-related node genes in prostate cancer

目的:同源框基因NKX3.1与前列腺癌发生和进展关系密切,本研究探索前列腺癌中NKX3.1调控的相关下游节点基因及可能的调控机制。方法:首先对前列腺癌相关的公开数据库进行生物信息多组学数据分析,筛选出与NKX3.1可能相关的5个下游信号通路节点基因;利用NKX3.1表达载体转染前列腺癌细胞系PC-3,实现NKX3.1在前列腺癌细胞过表达,通过Real-Time PCR验证上述节点基因转录水平表达改变。结果:经过生物信息多组学分析,筛选出在前列腺癌中与NKX3.1密切相关的信号通路节点基因MAZ、LPAR3、TUBB2A、CAMKK2和CPT1B。细胞水平验证实验表明,在NKX3.1过表达的前列腺癌细胞PC-3中表达显著变化(变化倍数>3)的基因有CPT1B(上调4.641倍)、CAMKK2(上调3.439倍)、MAZ(下调5.236倍)。结论:NKX3.1可能通过下调MAZ、诱导CAMKK2和CPT1B表达抑制前列腺癌的发生或进展,其中可能通过CAMKK2下游调控通路及CPT1B参与调节前列腺癌代谢过程。

Objective： The NKX3.1 homeobox gene is closely associated with the development and progression of prostate cancer. This study was to explore NKX3.1-related down-stream node genes and their possible regulating mechanisms in prostate cancer. Methods： By multi-omics analysis of the TCGA data on prostate cancer,we screened 5 node genes in the down-stream signaling pathways that were possibly related to NKX3.1.We achieved the overexpression of NKX3.1 in prostate cancer by transfecting the prostate cancer PC-3 cell lines with the NKX3.1 expression vector and determined the expression levels of the node genes by real-time PCR. Results： Based on the results of multi-omics analysis,MAZ,LPAR3,TUBB2A,CAMKK2 and CPT1B were identified as the node genes involved in the NKX3.1-related signaling pathways in prostate cancer. The NKX3.1 overexpression experiments showed that the CAMKK2 and CPT1B genes were up-regulated 3. 439 and 4. 641 times respectively and the MAZ gene down-regulated 5.236 times in the prostate cancer PC-3 cells with the overexpression of NKX3.1. Conclusion： NKX3.1 may suppress the development and progression of prostate cancer by down-regulating the expression of MAZ and up-regulating those of CAMKK2 and CPT1B,and it may also be involved in the regulation of the metabolic process of prostate cancer through the CAMKK2 down-stream signaling pathway and CPT1B.