<p>PIM3 Promotes the Proliferation and Migration of Acute Myeloid Leukemia Cells</p>

Abstract

Purpose Acute myeloid leukemia (AML) is associated with a poor overall prognosis. PIM family genes, including PIM1, PIM2 , and PIM3 , are proto-oncogenes that are aberrantly overexpressed in different types of human cancers. In this study, we aimed to explore and clarify the function of PIM3 in AML. Patients and Methods The expression of the three PIM genes in AML was detected using the Gene Expression Omnibus. The expression of PIM3 and PIM3 in patient samples and AML cell lines was measured using quantitative real-time polymerase chain reaction or Western blot analyses. The cellular behaviors of PIM3 -overexpressing AML cell lines were detected using a CCK-8 assay, flow cytometry, Western blotting, immunofluorescence staining, and a cell migration assay. The interactions between PIM3 and phosphorylated CXCR4 (pCXCR4) were explored via immunoprecipitation. Results Higher PIM3 expression was detected in primary AML cells than in healthy donor cells. Second, PIM3 overexpression promoted AML cell proliferation and protected against spontaneous apoptosis by phosphorylating BAD (pBAD) at Ser112. Furthermore, PIM3 overexpression might promote the migration of AML cells via CXCR4. PIM3 -overexpressing AML cell lines exhibited increased CXCR4 phosphorylation at Ser339, and pCXCR4 interacted with PIM3. Conclusion Our findings suggest that PIM3 regulates the proliferation, survival, and chemotaxis of AML cell lines. Moreover, pCXCR4 might mediate the regulation of PIM3-induced chemotaxis. Therefore, the inhibition of PIM3 expression may be a promising therapeutic target in AML.

Long non-coding RNA (FALEC) promotes malignant behaviors of gastric cancer cells by regulating miR-203b/PIM3 axis

“…Besides, through bioinformatics analysis, we also discovered that there were the binding sites between microRNA-203b (miR-203b) and Recombinant Pim-3 Oncogene (PIM3), suggesting that miR-203b may target PIM3. Several studies have also uncovered that PIM3 acts as a carcinogen in various cancer processes (27)(28)(29). Therefore, we speculated that miR-203b/PIM3 axis plays a crucial role in the progression of GC.…”

GSK3 inhibitor suppresses cell growth and metabolic process in FLT3-ITD leukemia cells

“…However, these unaffected proteins were reported to be involved in the apoptosis of MV4-11 cells in other studies e.g. loss of ataxia telangiectasia mutated (ATM) mitigated the effect of miR-100 exhaustion on cell viability and apoptosis in AML cells [31], provirus integrating site moloney murine leukemia virus 3 (PIM3) overexpression enhanced AML cell proliferation and inhibited instinctive apoptosis by phosphorylating BAD (pBAD) at Ser112 [32], and Polyphyllin I affected the apoptosis of AML cell lines by regulating expression of phosphorylated-JNK [33]. Future studies are required to evaluate the precise mechanism underlying the effect of BIO on the apoptotic process and to identify downstream target proteins in the pathway triggering attenuated cell viability of AML cells with FLT3 mutation.…”

Targeting Pim kinases in hematological cancers: molecular and clinical review

“…Furthermore, an association between high Pim-1 expression and higher risk groups and overall survival was reported [ 80 , 81 ]. Pim-3 was also found to be over-expressed in the bone marrow derived samples from AML patients [ 82 ]. The difference in expression levels observed in different studies could be due to the lack of direct correlation between Pim-1 gene and protein levels, or to the fact that Pim-1 is not expressed in early, non-treated AML blasts, whereas Pim-1 is up-regulated in late stage, more aggressive cases.…”