Profilin 1 induces drug resistance through Beclin1 complex‐mediated autophagy in multiple myeloma |
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| Authors: | Yichen Lu Ya Wang He Xu Chen Shi Fengyan Jin Wei Li |
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| Affiliation: | 1. Cancer Center, the First Bethune Hospital of Jilin University, Jilin, China;2. Department of Respiratory Medicine (Department of Respiratory and Critical Care Medicine), National Key Clinical Specialty, Xiangya Hospital, Central South University, Hunan, China |
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| Abstract: | Autophagy plays an important role in multiple myeloma (MM) for homeostasis, survival and drug resistance, but which genes participate in this process is unclear. We identified several cytoskeleton genes upregulated in MM patients by gene expression profiling (GEP) datasets; in particular, patients with high profilin 1 (PFN1) expression had poor prognosis in MM. In vitro, overexpressed PFN1 promotes proliferation and bortezomib (BTZ) resistance in MM cells. Further study indicated overexpression of PFN1 significantly promoted the process of autophagy and induced BTZ resistance in MM. Otherwise, knockdown of PFN1 blocked autophagy and sensitized MM to BTZ. Co‐immunoprecipitation in MM cells indicated that PFN1 could bind Beclin1 complex and promote the initiation of autophagy. Inhibition of autophagy by blocking the formation of Beclin1 complex could reverse the phenotype of BTZ resistance in MM. Our findings suggested that PFN1 could promote autophagy through taking part in Beclin1 complex and contribute to BTZ resistance, which may become a novel molecular target in the therapy of MM. |
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| Keywords: | autophagy cell proliferation drug resistance multiple myeloma profilin |
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