Long noncoding RNAs (lncRNAs) have regulatory effects on gene expression. Dysregulation of lncRNAs has an essential impact on the transcriptome, influencing cellular functions and behaviors. High expression of lncRNA AFAP1-AS1 has been widely reported in lung adenocarcinoma (LUAD). The purpose of this study was to predict some of the differentially expressed genes (DEGs) by which AFAP1-AS1 can influence the transcriptome in LUAD. R software was used to determine the DEGs from TCGA-LUAD expression data. It was focused on DEmRNAs that may be directly (mRNA-lncRNA) or indirectly (TFs- or miRNAs-lncRNA) influenced by AFAP1-AS1 according to the RNAInter, TRRUST, and miRTarBase databases. Approximately, 1584 DEmRNAs could be influenced by AFAP1-AS1 in LUAD. Cell cycle and cellular senescence were the most significant enriched pathways of the 1584 DEmRNAs. In the transcription regulatory network, several overexpressed oncogenes such as CCNE1, BIRC5, CDK1, MMP9, and MMP1 were identified as diagnostic biomarkers based on ROC curve analysis. AFAP1-AS1 competing endogenous RNA (ceRNA) network included 5 low-expressed miRNAs and 12 high-expressed mRNAs (such as CDK1). It was found significant correlations between the expression of AFAP1-AS1 related DEmRNAs such as MMP9 and MMP1 (metastatic genes) and tumor infiltration of the cancer-associated fibroblast in LUAD based on the TIMER2.0 database. The results of this study highlight AFAP1-AS1 effect on cell cycle and metastasis and provide new insights into how highly expressed AFAP1-AS1 acts as an oncogene and could be considered as a therapeutic target in LUAD.