Zeng Lirong, Zeng Guilin, Ye Zhong
Chengdu Railway Health School, Chengdu, China.
Chengdu Fifth People's Hospital, Chengdu, China.
Appl Bionics Biomech. 2022 May 31;2022:9268206. doi: 10.1155/2022/9268206. eCollection 2022.
To explore the differentially expressed microRNAs (DEmiRs) derived from plasma exosomes related to radiotherapy resistance and their corresponding pathways in non-small-cell lung cancer (NSCLC).
Plasma samples from NSCLC patients were retrieved and analyzed. The patients were divided into 3 groups based on the tumor regression grade criteria, assessed by radiological imaging after radiotherapy. TRG1 referred to tumor shrinkage of ≤30% after radiotherapy, TRG2 as 30% < TRG < 50%, and TRG3 as TRG ≥ 50%. High-throughput sequencing and bioinformatics analysis were used to compare the DEmiRs between the three groups. The miRanda, PITA, and RNAhybrid software were used to identify potential target genes of the DEmiRs. GO function enrichment and KEGG pathway enrichment analyses were performed on the target gene set.
There were 24 DEmiRs (12 were upregulated and 12 downregulated) between the TRG1 and TRG2 groups, 11 between the TRG1 and TRG3 groups (6 upregulated and 5 downregulated), and 35 between the TRG2 and TRG3 groups. The common DEmiRs between the three groups were miR-92a-3p. GO analysis showed that the target genes of the DEmiRs were mainly enriched in unicellular organism processes, cell transformation, cell localization, and their establishment. KEGG enrichment analysis showed that target genes were significantly enriched in the Ras signaling pathway and associated with endocytosis. Among the 135 identified target genes of miR-92a-3p, 4 were involved in the PI3K-Akt signaling pathway (the downstream pathway of the Ras gene) and 3 in the cAMP signaling pathway (the upstream pathway of the Ras gene). Further, 2 other target genes were involved in the Rap1 signaling pathway (the upstream pathway of PI3K-Akt).
By assessing the expression and functional profile of DEmiRs in the plasma exosomes of NSCLC patients after radiotherapy, miR-92a-3p was identified as a promising target affecting radiotherapy outcomes through the Ras signaling pathway.
探讨非小细胞肺癌（NSCLC）患者血浆外泌体中与放疗抵抗相关的差异表达微小RNA（DEmiRs）及其相应通路。
收集并分析NSCLC患者的血浆样本。根据放疗后影像学评估的肿瘤退缩分级标准，将患者分为3组。TRG1指放疗后肿瘤缩小≤30%，TRG2为30%＜TRG＜50%，TRG3为TRG≥50%。采用高通量测序和生物信息学分析比较三组之间的DEmiRs。使用miRanda、PITA和RNAhybrid软件鉴定DEmiRs的潜在靶基因。对靶基因集进行GO功能富集和KEGG通路富集分析。
TRG1组与TRG2组之间有24个DEmiRs（12个上调，12个下调），TRG1组与TRG3组之间有11个（6个上调，5个下调），TRG2组与TRG3组之间有35个。三组之间的共同DEmiR为miR-92a-3p。GO分析表明，DEmiRs的靶基因主要富集于单细胞生物过程、细胞转化、细胞定位及其建立。KEGG富集分析表明，靶基因在Ras信号通路中显著富集，并与内吞作用相关。在miR-92a-3p的135个已鉴定靶基因中，4个参与PI3K-Akt信号通路（Ras基因的下游通路），3个参与cAMP信号通路（Ras基因的上游通路）。此外，另外2个靶基因参与Rap1信号通路（PI3K-Akt的上游通路）。
通过评估NSCLC患者放疗后血浆外泌体中DEmiRs的表达和功能谱，miR-92a-3p被鉴定为一个有前景的靶点，其通过Ras信号通路影响放疗结果。
