LIFR expression

The results revealed that hsa_circ_0072309 overexpression suppressed HCC cell proliferation, migration, invasion, and sorafenib resistance, whereas its suppression showed opposite results...In turn, hsa_circ_0072309 recruited the E1A binding protein p300 to promote the enrichment of H3K27 acetylation (H3K27ac) in the LIFR enhancer, thus transcriptionally promoting LIFR expression. To conclude, we revealed a hsa_circ_0072309/LIFR regulatory loop in HCC, which may provide a potential target for HCC treatment.

In patient-derived organoids (hPDOs) from GC patients, GDCA reverses LIF-induced stemness and proliferation. In summary, we have identified the secondary bile acids as the first endogenous antagonist to LIFR supporting a development of bile acid-based therapies in LIF-mediated oncogenesis.

Finally, GC's high LIFR expression was associated with better clinical outcomes in patients. LIF treatment could thus represent a targeted anti-CSC strategy to fight against metastatic GC, and LIFR detection in primary tumours could constitute a potential new prognosis marker in this disease.

Dual luciferase reporter assay verified that IRF1 could transactivate LIFR transcription by binding to its promoter. In conclusion, IFN-τ can induce IRF1 expression in bovine endometrial epithelial cells, and IRF1 upregulates LIFR expression by binding to LIFR promoter, contributing to the enhancement of bovine endometrial receptivity.

Additionally, our bioinformatic analysis reveals a signature of transcriptional regulation associated with FAM3C/LIFR interaction and identifies the TWIST1 transcription factor as a downstream effector that participates in the maintenance of LIFR expression. Finally, we characterize the effect of LIFR expression in cell-based experiments that demonstrate the promotion of invasion, migration, and self-renewal of breast cancer stem cells (BCSCs), consistent with previous studies linking LIFR expression to tumor initiation and metastasis in mammary epithelial cells.

Overexpression of LIFR suppressed the migration and invasion of UCEC cells in vitro. Our pan-cancer detection data provided a novel understanding of the roles of LIFR in oncogenesis.

The tumorigenicity assay showed that circ_0003159 overexpression inhibited tumor growth in vivo. In conclusion, circ_0003159 inhibited GC development in vitro and in vivo by enriching the level of LIFR via direct binding to miR-221-3p/miR-222-3p.

Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on HCC patient-derived xenograft tumors with low LIFR expression and high LCN2 expression. Thus, anti-LCN2 therapy is a promising way to improve liver cancer treatment by targeting ferroptosis.

In a second model of LIFR repression, in which parathyroid hormone-related protein (PTHrP) suppresses LIFR expression, we found that PTHrP binds to the distal LIFR promoter, and that PTHrP suppression of LIFR protein is similarly reversed by HDAC inhibitor treatment. Together, these data suggest that HDAC inhibitors stimulate LIFR regardless of the way it is repressed by the microenvironment.

Recent Phase II clinical trial data studying entinostat and azacitidine in metastatic breast cancer revealed that induction of several pro-dormancy genes post-treatment was associated with prolonged patient survival. Together, these findings suggest HDACi as a potential therapeutic avenue to promote dormancy, prevent recurrence, and improve patient outcomes in breast cancer.

Lidocaine might GC cell malignancy by modulating circ_ANO5/miR-21-5p/LIFR axis, highlighting a novel insight for GC treatment.

These results indicate that the LIFR/STAT3 pathway may mediate either tumor promoting or tumor suppressive signaling pathways depending on the genetic background of tumor cells, and may play diverse roles within other cells in the tumor microenvironment. Implications: Mutant KRAS drives downregulation of the receptor for leukemia inhibitory factor, thereby allowing an increase in expression of the glucose transporter GLUT1 and increases in glycolysis and mitochondrial respiration.

circ_0001073 increased LIFR expression via miR-626 in lung cancer cells. In conclusion, circ_0001073 represses lung cancer progression via miR-626/LIFR axis, indicating the potential value of circ_0001073 in lung cancer treatment.

LIF was up-regulated and high LIF expression was associated with poor prognosis while LIFR was down-regulated and high LIFR expression was associated with favorable prognosis in pancreatic adenocarcinoma. LIF and LIFR might be therapeutic targets and prognostic markers for individual therapy of pancreatic adenocarcinoma.

Overall, the results demonstrate that LIF promotes the malignant biological behavior of GC cells through LIFR-Hippo-YAP signaling. LIF may therefore be a useful biomarker for GC.

Eight cohorts containing 1278 cases with PAAD were identified and the analysis results suggested that LIF was highly expressed while LIFR was lowly expressed in PAAD tissues compared with adjacent or normal tissues. Kaplan-Meier plot curves and univariate and multivariate Cox proportional hazards regression analyses indicated high LIF expression was associated with shorter overall survival (adjusted hazard ratio = 1.641, 95% CI: 1.399-1.925, p < 0.001) whereas high LIFR expression was associated with longer overall survival (adjusted hazard ratio = 0.653, 95% CI: 0.517-0.826, p < 0.001).

High LIF/LIFR levels indicated shorter biochemical recurrence-free survival among patients who underwent radical prostatectomy. Therefore, the lncAMPC/LIF/LIFR axis plays a critical role in PCa metastasis and immunosuppression and may serve as a prognostic biomarker and potential therapeutic target.

These results demonstrated that low LIFR expression reduces the neuroprotective efficacy of LIF in aged rodents of both sexes. Furthermore, the ability of LIF to promote motor improvement is dependent upon sex in aged rodents.