KL overexpression

In renal tubular epithelial cells, knockdown of Klotho and overexpression of FGF23 increased the expression of inflammatory factors; however, their levels were significantly lower than that of the Klotho knockdown group. Collectively, these findings demonstrate that in CKD, the FGF23-Klotho axis promotes the expression of inflammatory cytokines in renal tubular epithelial cells.

The present study elucidates the mechanisms underlying this role and highlights the potential of the CRISPR/Cas9 system as a gene editing tool in cancer research. Our data suggest that activation of the KL gene may serve as a novel therapeutic strategy and biomarker for studies in colorectal cancer.

Interestingly, KL-high/-rearranged cases seemed to form a clinicopathologically homogeneous group, showing a predilection for skeletal/sinonasal locations and typically matrix-poor, cellular solitary fibrous tumor-like morphology. Importantly, FGFR1 signaling pathways were upregulated in fusion-negative PMTs regardless of the KL status compared with non-PMT mesenchymal tumors by gene set enrichment analysis, perhaps justifying FGFR1 inhibition in treating this subset of PMTs.

We show treatment of these cells with AGTR1 inhibitor losartan, or silencing of the Agtr1 gene leads to increased cell death in vitro and attenuates tumor progression in vivo...Therefore, we conclude that Agtr1 and Klotho are important for TSC2-deficient cell survival. These findings further illuminate the role of the renin-angiotensin system in LAM and the potential of targeting Agtr1 inhibition in TSC2-deficient cells.

We investigated in depth the mechanism of β-Klotho regulating CSF-1 secretion and found that β-Klotho inhibits the phosphorylation of p65, which blocked the nuclear translocation of p65, thereby inhibiting the secretion of CSF-1 by EC cells. The above results indicate that β-Klotho-mediated inhibition of CSF-1 secretion reduces the migration of macrophages to tumor tissue and delays the progression of EC.

The increased amount of cells with activated caspases and annexin V (p < 0.001) corresponded with the expression of secreted Klotho. This mechanism, as suggested, maybe causative of the observed effects.

Our results indicate that overexpression of Klotho gene in Caco-2 cells via CRISPR/Cas9-sensitized TRAIL death receptor DR4 suppresses the proliferation of cells by leading to apoptosis. Thus, this study conducted on apoptosis-resistant colon cancer cells may bring new insights about the role of Klotho gene in colon cancer.

βKlotho inhibits proliferation of prostate cancer cells by downregulating ELK4. Both βKlotho and ELK4 expressions correlate with the prognosis of PCa, which may serve as potential biomarkers for follow-up surveillance and prognostic assessments.

However, injection of the Wnt/β-catenin pathway activator attenuated the effects of Klotho overexpression. Klotho inhibits cell proliferation in RET fusion models of PTC by inhibiting the Wnt/β-catenin pathway, providing a potential target for developing treatment for PTC.