The role of KIAA1191 in the necroptotic pathway of multiple myeloma.

Multiple myeloma (MM) is an incurable plasma cell malignancy, and International Staging System (ISS) is used to predict the outcomes of MM patients. However, ISS stage is imperfect, and there might exist other factors correlated with prognosis of MM patients. Expression profiles and clinical information of 340 newly diagnosed MM patients from GEO database and 105 newly diagnosed MM patients from our hospital were analyzed, and LASSO regression was used to screen genes associated with both overall survival and progression-free survival of MM patients. Nomogram was constructed to predict outcomes of MM patients. Then, CCK8 and transwell assays were used to evaluate the proliferation and migration ability of MM cells; flow cytometry was performed to verify whether MM cells underwent necroptosis. Quantitative real-time PCR and western blot were performed to evaluate gene expressions. We found that KIAA1191 was associated with both overall survival and progression-free survival of MM patients. Furthermore, KIAA1191 high expression suppressed the proliferation and migration of MM cells; upregulated the expression of RIP1, RIP3, and CYLD, and restored the TNF-α/z-VAD-induced necroptosis. Besides, KIAA1191 overexpression had a synergistic effect with bortezomib on the proliferation capability of MM cells.