biostudies-literatureLiu YNational Natural Science Foundation of Chinathe General Research Fund, Research Grants Council of Hong Kong3288-3304https://www.ebi.ac.uk/biostudies/studies/S-EPMC11447899biostudies-literatureUnknown115(10)KRAS gene mutations are common in pancreatic ductal adenocarcinoma (PDAC), but targeting mutant KRAS is still challenging. Here, an endoribonuclease-prepared small interfering RNA (esiRNA) library was used to screen new kinases that play critical roles in PDAC driven by KRAS gene mutations, and serine/threonine kinase 31 (STK31) was identified and characterized as a potential therapeutic target for KRAS-mutant PDAC. Our results showed that STK31 was upregulated in KRAS-mutant PDAC patients with poor survival and highly expressed in PDAC cell lines with KRAS^G12D mutation. Inhibition of STK31 in KRAS-mutant cell lines significantly reduced PDAC cell growth in vitro and hindered tumor growth in vivo. Gain and loss of function experiments revealed that STK31 is a downstream target oCancer scienceThe molecular mechanism underlying KRAS regulation on STK31 expression in pancreatic ductal adenocarcinoma.PMC11447899CUHK1412041932270618CUHK14120618CUHK14171217Liu YWong CHTo KFTang SCChan SLLi CHChen YLi BfalseThe molecular mechanism underlying KRAS regulation on STK31 expression in pancreatic ductal adenocarcinoma.KRAS gene mutations are common in pancreatic ductal adenocarcinoma (PDAC), but targeting mutant KRAS is still challenging. Here, an endoribonuclease-prepared small interfering RNA (esiRNA) library was used to screen new kinases that play critical roles in PDAC driven by KRAS gene mutations, and serine/threonine kinase 31 (STK31) was identified and characterized as a potential therapeutic target for KRAS-mutant PDAC. Our results showed that STK31 was upregulated in KRAS-mutant PDAC patients with poor survival and highly expressed in PDAC cell lines with KRAS^G12D mutation. Inhibition of STK31 in KRAS-mutant cell lines significantly reduced PDAC cell growth in vitro and hindered tumor growth in vivo. Gain and loss of function experiments revealed that STK31 is a downstream target o2024-01-01T00:00:00Z2024 Oct2025-04-05T08:57:37.079Z2025-04-05T08:57:37.079ZS-EPMC114478993905479710.1111/cas.16286