RIOK 1 is associated with non-small cell lung cancer clinical characters and 1 contributes to cancer progression 2

31 Lung cancer is one of the most common malignant tumors and is currently the leading 32 cause of cancer-related deaths worldwide. Although the treatment strategy has been 33 significantly improved, the prognosis of lung cancer patients is still quite poor. 34 RIOK1 has been reported to be highly expressed in non-small cell lung cancer 35 (NSCLC), however, its clinical significance and biological function are still largely 36 unknown in lung cancer. Using western blot and immunohistochemistry, we showed 37 that RIOK1 was highly expressed in NSCLC tissues and correlated with advanced 38 stage and poor prognosis. Furthermore, knockdown of RIOK1 could inhibit 39 proliferation, migration, and invasion in NSCLC cells and tumorigenesis in vivo 40 through AKT, Cyclin B1, MMP2, and EMT pathway. Furthermore, cell viability and 41 apoptosis assays demonstrated that RIOK1 maintained NSCLC cell survival and 42 reduced apoptosis rate when cells were treated with cisplatin. Western blot analysis 43 demonstrated that RIOK1 depletion caused up-regulated protein expression of cleaved 44 PARP and Caspase-3 in NSCLC cells. These findings revealed a novel function of 45 RIOK1 in non-small cell lung cancer progression and suggest that RIOK1 might 46 become a promising diagnostic and therapeutic target for this disease. 47 Key word: RIOK1, non-small cell lung cancer, proliferation, invasion, chemical 48