FOSL1 drives the malignant progression of pancreatic cancer cells by regulating cell stemness, metastasis and multidrug resistance

Background Targeted therapy is a key strategy for the treatment of advanced and metastatic pancreatic cancer, one of the leading causes for cancer-related death worldwide. To address the limitations of existing targeted drugs, there is an urgently need to find novel targets and therapeutic strategies. Transcription factor FOSL1 is a potential therapeutic target for challenging pancreatic cancer, which contributes to the malignant progression and poor gnosis of pancreatic cancer. Methods Human FOSL1 complete RNA, shRNA against FOSL1 and shRNA against HMGA1 lentiviral recombination vectors were used to overexpress FOSL1 and knock down FOSL1 and HMGA1. RNA sequencing, Q-PCR and Western blots were used to investigate the effects of FOSL1 on the proliferation of pancreatic cancer cells. The relationship between FOSL1 and HMGA1 were analyzed by co-IP Mass spectrometry, Q-PCR and Western blots. The regulatory roles of FOSL1 and HMGA1 in the invasion and migration, stemness, and multidrug resistance were determined by transwell assay, immunofluorescence, Q-PCR and Western blots. Results We found that FOSL1 promoted the proliferation and progression of pancreatic cancer by trigging stemness, invasion and metastasis, and drug resistance. HMGA1 was a key downstream target of FOSL1 and directly interacted with FOSL1. Knockdown of HMGA1 inhibited the proliferation of pancreatic cancer cells by regulating the expression of genes related to stemness, epithelial-mesenchymal transition and multidrug efflux system. FOSL1 promotes the proliferation of pancreatic cancer cells by up-regulating HMGA1 expression. Conclusion Targeting FOSL1 and HMGA1 in monotherapy or combination therapy is a promising strategy for the treatment of advanced and metastasis pancreatic cancer.