KLB (Klotho Beta)

In this research, results of western blotting and reactive oxygen species (ROS) assay demonstrated that knock down of KLB enhance the expression of TFRC, a driver gene of ferroptosis, thus blocking the ferroptosis inhibitory effect of FGF19. Based on these available evidence and data, we hypothesize that FGF19 signaling inhibit the ferroptotic cell death in HCC cells through FGFR4-KLB co-receptors, while suppression of FGFR4-KLB could block FGF19 signaling, thus trigger ferroptosis process.

KLB functions as a potential tumor suppressor in CRC, with diagnostic, prognostic, and therapeutic implications. Its expression in stromal components of the tumor microenvironment suggests a regulatory role in immune response and tumor progression. These findings support KLB as a promising biomarker and therapeutic target for CRC.

In mediation analysis, decreased chymotrypsin B2 (CTRB2) levels mediated 1.03% (95% CI [confidence interval] 0.02%-2.03%) of the effects of body mass index on acute pancreatitis...We also found increased klotho beta (KLOTB) levels mediated the effects of waist-hip ratio (7.01%, 95% CI 3.30%-10.71%) and visceral adipose tissue (8.98%, 95% CI 4.55%-13.41%) on chronic pancreatitis, and decreased receptor tyrosine kinase-like orphan receptor 1 (ROR1) levels mediated the effects of body mass index (10.39%, 95% CI 3.36%-17.42%) and visceral adipose tissue (6.29%, 95% CI 1.00%-11.58%) on pancreatic carcinoma. The MR suggests that circulating CTRB2, RSPO3, KLOTB, and ROR1 proteins may mediate associations between obesity and pancreatic diseases.

These results underscore the importance of KLB in the course and management of HNSC by indicating that it may function as a possible prognostic marker and influence immunological and therapeutic responses in these individuals. Further study on HNSC is necessary to investigate KLB's potential as a therapeutic target and prognostic indicator.

Serum KLB level is associated with the severity of HBV-related liver diseases and has important diagnostic value for HCC. Therefore, it could be a predictive biomarker for monitoring disease progression.

In-depth research on its processing methods, active ingredients, quality control, pharmacokinetics, pharmacological and toxicological mechanisms, and standardized clinical application is needed. This paper provides a reference for the application and research of mirabilite in the future.

Taken together, this study has unveiled the tumor-promoting role of KLB mediated by its regulation on exosomes secretion through a Rab8a-dependent mechanism. These findings could be exploited to develop novel theranostic targets for prostate cancer.

Furthermore, the results revealed that HDAC3 inhibitor‑mediated acetylated modification led to KLB inactivation, resulting in the blockade of FGF21‑KLB signaling, which further triggered the expression of EMT induction‑related genes in Huh7 cells. In conclusion, the present study demonstrated that aberrant acetylated modification of KLB inhibited FGF21‑KLB signaling, thereby promoting β‑catenin signaling‑driven EMT and HCC metastasis.

Genome-wide CRISPR loss-of-function screening revealed that FGFR3 restricted the activity of FGFR4-selective inhibitors in inducing cell death; the pan-FGFR inhibitor erdafitinib displayed superior potency than FGFR4-selective inhibitors in suppressing the growth and survival of FGF19-positive HCC cells. Among FGF19-positive HCC cases from The Cancer Genome Atlas (TCGA), FGFR3 is prevalently coexpressed with FGFR4 and KLB, suggesting that FGFR redundancy may be a common mechanism underlying the de novo resistance to FGFR4 inhibitors. Our study provides a rationale for clinical testing of pan-FGFR inhibitors as a treatment strategy for FGF19-positive HCC.