PIM1 overexpression

PIM1 alleviated mice liver oxidative stress and NAFLD induced by High-fat diet by regulating the NRF2/HO-1/NQO1 signaling Pathway.

Erastin treatment reversed the impacts of PIM1 on hRMECs, suggesting the mediation of ferroptosis in PIM1 regulation. The current study has yielded critical insights into the role of PIM1 in ameliorating high glucose-induced hRMEC dysfunction through the inhibition of ferroptosis.

In RCC cell lines, IL-6 blockade through either anti-IL-6 antibody or tocilizumab was sufficient to decrease PIM1 protein levels. Treatment with ruxolitinib leads to a dose and time-dependent decrease in PIM1 levels... These results suggest that differential expression of PIM1 in RCC may be linked to autocrine IL-6 signaling. Furthermore, poor survival in PIM1-overexpressing RCC patients is independent of treatment received, and therefore necessitates use of targeted therapies against this axis. Multiple FDA-approved agents are available that target this pathway.

PIM1 inhibitor AZD1208 was used to inhibit PIM1 and PIM1-experssing adenovirus was used to overexpress PIM1. This study demonstrated the protective effect of PIM1 in cisplatin-induced AKI, and regulation of Drp1 activation might be the underlying mechanism. Altogether, PIM1 may be a potential therapeutic target for cisplatin-induced AKI.

Our data suggest a strong association between PIM expression and increased MAPK activation score, T cell inflamed score, inflammatory, MHC class I and MHC class II gene expression, and differential immune cell infiltration. A better understanding of these differences will provide a rationale for tailored therapeutic approaches for PIM-expressing PC.

In vivo smooth muscle invasion assays showed that overexpression of PIM1 significantly increased the depth of tumor cell invasion, and treatment with PIM inhibitors significantly reduced intramuscular PCa invasion. This research uncovers a HIF-1-independent signaling axis that is critical for hypoxia-induced invasion and establishes a novel role for PIM1 as a key regulator of the actin cytoskeleton.

AZD1208 (a PIM1 inhibitor) aggravated renal IRI, while PIM1 overexpression ameliorated renal IRI...Moreover, results demonstrated that ASK1 was a downstream target of PIM1 by administering Selonsertib (an inhibitor of ASK1 activity), and inhibiting ASK1 alleviated cell death after HR in PIM1 knockdown cells by reducing JNK/P38 activation. In conclusion, this study elucidated the protective effect of PIM1 on renal IRI, and the underlying mechanism may be related to ASK1-JNK/P38 signaling pathway. Taken together, PIM1 may be a potential therapeutic target for renal IRI.

Moreover, the oral administration of SGI-1776 significantly suppressed subcutaneous ARK1 xenograft tumor growth in nude mice without impairing health. These results indicate that PIM1 is involved in the acquisition of aggressiveness and suggest the potential of PIM1 as a novel therapeutic target and SGI-1776 as a therapeutic agent for SC.

To identify transcriptional gene programs driving persistent lung fibrosis in aging, we performed RNA-Seq on lung fibroblasts isolated from young and aged mice during the early resolution phase after bleomycin injury...Pharmacological inhibition of PIM1 attenuated IPF fibroblast activation and sensitized them to apoptotic stimuli. Inhibition of PIM1 signaling in IPF lung explants ex vivo inhibited pro-survival gene expression and collagen secretion, suggesting that targeting this pathway may represent a therapeutic strategy to block IPF progression.

In vivo experiments showed that Ventilagolin could effectively suppress HCC tumor growth, downregulate Pim-1, N-cadherin and Vimentin expression, and upregulate E-cadherin expression. Ventilagolin suppresses HCC cell proliferation, migration and invasion and reverses EMT process by downregulating Pim-1, suggesting Ventilagolin is a potential therapeutic agent for treatment of HCC.

We also use rapid immunoprecipitation and mass spectrometry of endogenous proteins on chromatin (RIME), to find that select AR co-regulators, such as hnRNPK and TRIM28, interact with both AR and 14-3-3 ζ in PIM1 over-expressing cells. We conclude that PIM1 phosphorylation of AR and 14-3-3 ζ coordinates their interaction, which in turn recruits additional co-regulatory proteins to alter AR transcriptional activity.

Furthermore, an inverse correlation between PIM1 mRNA expression levels and miR-3135b expression was observed in clinical samples. Therefore, the present study identified miR-3135b as a novel regulator of 5-FU sensitivity in CRC.

Our findings suggest that identified phytoconstituents Dehydrotectol and Nordracorubin bind to PIM1 in ATP-competitive binding mode. These findings and the compounds reported herein warrant further exploration as promising scaffolds for anticancer drug design, discovery, and development.

More importantly, Pim1 inhibitor overcame the resistance of breast cancer cells to HER2 tyrosine kinase inhibitor lapatinib. In summary, downregulation of HER2 by targeting Pim1 may be a promising and effective therapeutic approach not only for anti-cancer growth but also for circumventing lapatinib resistance in HER2-positive breast cancer patients.

We demonstrated that while bleomycin-induced lung fibrosis in young mice is self-resolving, aged mice exposed to bleomycin developed sustained lung fibrosis, evidenced by enhanced collagen deposition and accumulation of fibroblasts which fail to undergo apoptosis...Knockdown of PIM1 using RNAi or inhibition of its kinase activity using the inhibitor AZD1208 in IPF fibroblasts reduced TGFβ- and PDGF-BB-induced differentiation and proliferation, respectively... PIM1 expression is elevated in lung fibroblasts from aged mice that failed to undergo fibrosis resolution following lung injury. Elevated PIM1 expression in human lung fibroblasts potentiates their fibrogenic activation and desensitizes them to apoptosis. Targeting PIM1 may serve as a strategy to sensitize pathogenic fibroblasts to apoptosis and promote lung fibrosis resolution.

Co-expression of AR and PIM1 exists in only in a small percentage of patients with TNBC. The implications of this finding in the therapeutic management of patients with TNBC should be investigated in larger patient cohorts.