Pancreatic adenocarcinoma (PAAD), accounting for 85 % of pancreatic cancer, is one of the most malignant and prevalent tumors worldwide, with a 5-year survival of approximately 10 % (Chen et al., 2016, Sung et al., 2021, Wood et al., 2022). The poor prognosis of PAAD patients is mostly due to its advanced stage at diagnosis, its aggressive nature, and its extensive resistance to conventional therapeutics, e.g., chemotherapy, radiotherapy, and molecularly targeted therapy (Kleeff et al., 2016). Hence, a more thorough understanding of the molecular mechanisms underlying the tumorigenesis and progression of PAAD is warranted. Efforts invested in discovering novel oncogenes in PAAD will help pave the way for developing more effective anticancer therapeutics and prognostic biomarkers for patients with PAAD, which subsequently would improve their survival remarkably.

Rho GTPases-activating proteins (RhoGAPs) are emerging as biomarkers for multiple tumors and are considered tumor suppressors in general (Csepanyi-Komi et al., 2013, Kandpal, 2006). For instance, ARHGAP25 was down-regulated in PAAD and the silencing of ARHGAP25 activated AKT/mTOR signaling to promote glycolysis and proliferation in PAAD cells (Huang et al., 2021). Decreased expression of ARHGAP10 had been found to correlate with poor prognosis of ovarian cancer. Further study indicated that overexpression of ARHGAP10 significantly suppressed the adhesion, migration, and invasion of ovarian cancer cells (Luo et al., 2016). However, ARHGAP11A is more commonly known as an oncogenic GAP in cancers. Researchers have identified that ARHGAP11A was overexpressed in basal-like breast cancer cells, and ARHGAP11A knockdown led to CDKN1/p27-mediated cell cycle arrest (Lawson et al., 2016). In hepatocellular carcinoma, upregulation of ARHGAP11A promoted the proliferation, invasion, migration, and epithelial-mesenchymal transition of cancer cells in vitro, while downregulation of ARHGAP11A reduced cell growth and metastasis in vivo (Dai et al., 2018). Similarly, the expression of ARHGAP11A was increased in gastric cancer cells and the interaction between ARHGAP11A and TPM1 facilitated the malignant progression of gastric cancer by regulating cell migration and invasion (Guan et al., 2021). Nevertheless, there is little knowledge about the biological functions of ARHGAP11A in PAAD.

In this study, we investigated the expression level of ARHGAP11A in PAAD and assessed its prognostic value, which indicated the potential oncogenic role of ARHGAP11A. The subsequent RNA-seq of ARHGAP11A-deficient PAAD cells suggested that ARHGAP11A was closely related to cell proliferation, cell cycle, and apoptosis of PAAD cells. Functional enrichment analyses of The Cancer Genome Atlas (TCGA)-PAAD dataset yielded similar results. More importantly, biological experiments further confirmed that ARHGAP11A could significantly promote the proliferation, cell cycle progression, and apoptosis resistance of PAAD cells. Taken together, our study indicated that ARHGAP11A might function as an oncogene in PAAD, which would lay the foundation for the development of ARHGAP11A-targeted therapy for PAAD patients. The workflow of the study is shown in Fig. 1.