PIM1 overexpression in T-cell lymphomas protects tumor cells from apoptosis and confers doxorubicin resistance by upregulating c-myc expression

• DOI: 10.1093/abbs/gmy076
• Publication Date: 2018-06-08T19:09:05Z
• Authors: Xixi Xiang; Di Yuan; Yao Liu; Jiali Li; Qin Wen; Peiyan Kong; Lei Gao; Cheng Zhang; Li Gao; Xiangui Peng; Xi Zhang
• Keywords: STAT3 Transcription Factor; 0301 basic medicine; Antibiotics, Antineoplastic; Cell Survival; Apoptosis; Lymphoma, T-Cell; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; Proto-Oncogene Proteins c-myc; Jurkat Cells; 03 medical and health sciences; Proto-Oncogene Proteins c-pim-1; Doxorubicin; Drug Resistance, Neoplasm; Cell Line, Tumor; Humans; RNA Interference

T-cell lymphomas (TCLs) are a malignancy characterized by tumor aggression and resistance to traditional chemotherapy. Disruption of the extrinsic cell death pathway is essential for resistance to chemotherapy. PIM1 serves as a crucial modulator in cancers. However, the role of PIM1 in TCLs remains unclear. In this study, we studied the roles of PIM1 in established T-lymphoma cell lines Jurkat and HUT-78. CCK-8 assay was conducted to evaluate cell survival and flow cytometry was performed to evaluate cell death of TCL cells. siRNAs were used to knockdown the expression of PIM1 and c-myc. qRT-PCR was used to evaluate the mRNA expression levels of c-myc and PIM1. Western blot analysis was used to evaluate the protein expression levels of PIM1, c-myc, STAT3, and phospho-STAT3. Doxorubicin was used to determine the effect of PIM1 on apoptosis. Our results showed that PIM1 expression was markedly enhanced and induced c-myc expression in TCL cells. Doxorubicin inhibited the expressions of c-myc and PIM1, and triggered the extrinsic cell death of TCLs by suppressing the JAK-STAT3 signaling pathway. Moreover, PIM1 silencing via siRNA suppressed c-myc expression, promoted the cell death of TCLs, and increased doxorubicin sensitivity. Conversely, PIM1 overexpression in TCL cells induced c-myc expression, suppressed TCL cell death, and promoted doxorubicin resistance. Collectively, our results demonstrate that PIM1 overexpression in TCLs participates in cancer cell protection from apoptosis and leads to doxorubicin resistance by inducing c-myc expression, indicating that PIM1 may be a promising target in TCL treatment.