Poly-(A)-binding protein cytoplasmic 1 gene regulates cell proliferation via TP53 R273H hotspot activation in Japanese patients with common cancer types.

Mutations in TP53 occur in approximately half of all common cancer types and play a critical role in tumor progression and metastasis. However, because mutant TP53 can induce both loss- and gain-of-function effects, the development of drugs that directly target TP53 remains challenging. To identify downstream effectors of specific TP53 mutations, we compared gene expression profiles of colorectal (CRC), lung (LC), and stomach cancers (STC) carrying wild-type or mutant TP53. TP53 mutations were frequent (CRC 70.9%, LC 50.1%, STC 45.7%), with TP53-R273H being the most common. Comprehensive analyses comparing patients with TP53 mutations and those with wild-type TP53 identified 24 genes whose expression was significantly increased in TP53-mutated patients, and 20 genes whose expression was decreased across all three tumor types. Among them, PABPC1 showed significantly increased expression in A549 lung cancer cells and MCF7 breast cancer cells with wild-type TP53 transfected with TP53-R273H mutants. Silencing PABPC1 suppressed proliferation of TP53-R273H-mutant colon cancer cells (HT29, SW480). Additionally, patients with CRC harboring the TP53-R273H with high PABPC1 expression had poorer overall survival than those with low PABPC1 expression. These findings indicate that TP53-R273H upregulates PABPC1, suggesting that PABPC1 may function as an oncogene and represent a promising therapeutic target in patients with TP53-R273H mutation.