Mouse anti-Human STK3 monoclonal antibody, clone 5G8

Lupus nephritis (LN) is a typical characteristic of systemic lupus erythematosus. MicroRNAs (miRs) are reported to be involved in the onset and development of LN. The major purpose of the current study was to uncover the function of miR-9 in the pathogenesis of LN. Expression statuses of miR-9 and its potential target, STK3 in clinical samples were investigated. Then a dual firefly luciferase assay was conducted to reveal the regulating pattern of miR-9 on STK3. Human renal mesangial cells (HMCs) were employed to detect the effect of miR-9 down-regulated expression on viability and apoptosis in nephritis cells. The mechanism of miR-9 affecting LN was explored by measuring activities of STK3, ERK, JNK, and p38 in HMCs. It was found that miR-9 level was positively correlated with LN occurrence while STK3 was negatively correlated. Firefly luciferase assay demonstrated a negative regulation of miR-9 on STK3 transcription. Reduction of miR-9 significantly down-regulated cell viability and induced apoptosis in nephritis cells. The phenotypic changes in HMCs were accompanied by suppression of all the four studied indicators. The promoting function of miR-9 on LN was firstly elucidated in our study, and the molecule mechanism was the directly inhibition of STK3 transcription, which subsequently deactivated the downstream MAPKs.

Acute myeloid leukemia (AML) is characterized by a marked genetic heterogeneity, which complicates the development of novel therapeutics. The delineation of pathways essential within an individual patient's mutational background might overcome this limitation and facilitate personalized treatment. We report the results of a large-scale lentiviral loss-of-function RNA interference (RNAi) screen in primary leukemic cells. Stringent validation identified 6 genes (BNIPL1, ROCK1, RPS13, STK3, SNX27, WDHD1) whose knockdown impaired growth and viability of the cells. Dependence on these genes was not caused by mutation or overexpression, and although some of the candidates seemed to be rather patient specific, others were essential in cells isolated from other AML patients. In addition to the phenotype observed after ROCK1 knockdown, treatment with the approved ROCK inhibitor fasudil resulted in increased apoptosis and decreased viability of primary AML cells. In contrast to observations in some other malignancies, ROCK1 inhibition did not foster growth of immature malignant progenitors but was toxic to this cell fraction in feeder coculture and xenotransplant experiments, indicating a distinct effect of ROCK1 inhibition on leukemic progenitors. We conclude that large-scale RNAi screens in primary patient-derived cells are feasible and can complement other methods for personalized cancer therapies, such as expression and mutation profiling.