To date, increasing evidence has shown that ubiquitin E3 ligase and deubiquitination enzymes are directly involved in the regulation of tumor formation and metastasis of lung cancer, especially through the RAS-RAF-MEK-ERK and PI3K-AKT-mTOR signaling pathways, in which the ubiquitination of key signal nodes determines the biological and biochemical processes of tumor cells (Table 1). This evidence concerns the gene PIK3CA and neoplasm.