KLHL38 facilitates staurosporine‐induced apoptosis in HL‐1 cells via myocardin degradation

Abstract

Cardiac apoptosis has been identified as one of the main precipitating factors of heart failure (HF) throughout the whole course of progressive disease. Limited to the lack of diagnostic markers and effective drug targets, cardiac apoptosis is still a major clinical challenge. Here, we reveal a potential novel therapeutic target for cardiac apoptosis. In the cause of the study, we found that KLHL38 was highly expressed in cardiac tissue of HF patients via GEO data-mining, which was further verified in the heart tissue of transverse aortic constriction mice. Meanwhile, the expression of KLHL38 is negatively correlated with myocardin protein level, which is a key cardiac apoptosis regulator.The KLHL38 overexpression obviously promoted cardiomyocyte apoptosis treated with staurosporine by facilitation of myocardin's ubiquitylation and subsequent proteasomal degradation. These findings reveal a new therapeutic target, which may provide a new theoretical foundation for the treatment of myocardial apoptosis in clinical practice.

A Pan-cancer Analysis of Kelch Like Family Member 38 (KLHL38) Alterations in Human Cancers

“…From each sample, we extracted expression data for the gene ENSG00000175946 (KLHL38) as well as 150 marker genes from five immune pathways. (chemokines (41) receptors (18), MHC (21) immunoinhibitors (24), and immunostimulators (46)). [28] Samples from normal tissues and from the following sources were filtered out of the expression data, including Primary Solid Tumor, Primary Tumor, Primary Blood Derived Cancer -Bone Marrow, Primary Blood Derived Cancer -Peripheral Blood samples.…”

“…[23] In addition, KLHL38 is highly expressed in heart tissue of heart failure patients and it leads to cardiac apoptosis by promoting ubiquitination of myocardin. [24] It was reported that the overexpression of KLHL38 may indicate a poor prognosis for patients with non-small cell lung carcinoma (NSCLC) [25] and triple-negative breast cancer (TNBC) [26] due to its aggravated tumor behavior . In spite of this, studies on the role of KLHL38 in cancer were limited to certain types of tumors and no studies are available on pan-cancer.…”