FKBP10 promotes proliferation of glioma cells via activating AKT-CREB-PCNA axis

Abstract

Background Although the availability of therapeutic options including temozolomide, radiotherapy and some target agents following neurosurgery, the prognosis of glioma patients remains poor. Thus, there is an urgent need to explore possible targets for clinical treatment of this disease. Methods Tissue microarrays and immunohistochemistry were used to detect FKBP10, Hsp47, p-AKT (Ser473), p-CREB (Ser133) and PCNA expression in glioma tissues and xenografts. CCK-8 tests, colony formation assays and xenograft model were performed to test proliferation ability of FKBP10 in glioma cells in vitro and in vivo. Quantitative reverse transcriptase-PCR, western-blotting, GST-pull down, co-immunoprecipitation and confocal-immunofluorescence staining assay were used to explore the molecular mechanism underlying the functions of overexpressed FKBP10 in glioma cells. Results FKBP10 was highly expressed in glioma tissues and its expression was positively correlates with grade, poor prognosis. FKBP10-knockdown suppressed glioma cell proliferation in vitro and subcutaneous/orthotopic xenograft tumor growth in vivo. Silencing of FKBP10 reduced p-AKT (Ser473), p-CREB (Ser133), PCNA mRNA and PCNA protein expression in glioma cells. FKBP10 interacting with Hsp47 enhanced the proliferation ability of glioma cells via AKT-CREB-PCNA cascade. In addition, correlation between these molecules were also found in xenograft tumor and glioma tissues. Conclusions We showed for the first time that FKBP10 is overexpressed in glioma and involved in proliferation of glioma cells by interacting with Hsp47 and activating AKT-CREB-PCNA signaling pathways. Our findings suggest that inhibition of FKBP10 related signaling might offer a potential therapeutic option for glioma patients.

Transcriptomic Analysis of the Mechanisms for Alleviating Psoriatic Dermatitis Using Taodan Granules in an Imiquimod-Induced Psoriasis-like Mouse Model

“…To assess whether the remission of psoriatic lesions after TDG treatment may be due to the prevention of the over-proliferation of KCs, we verified the Ki67 and PCNA-positive cells in each group. Ki67 and PCNA are classical markers of cell proliferation in a variety of diseases ( Alhosaini et al, 2021 ; Cai et al, 2021 ). As expected, following TDG treatment, the number of Ki67 and PCNA-positive cells in IMQ-induced psoriasis-like mice decreased significantly ( Figure 2 ; Supplementary Figure S1 ), which is consistent with the results of previous studies ( Ru et al, 2020 ; Thatikonda et al, 2020 ; Tomalin et al, 2020 ).…”

Highly expressed of SERPINA3 indicated poor prognosis and involved in immune suppression in glioma

“…A previous study found that SERPINA3 promotes the proliferation of melanoma and human liver cancer cells 20,21 . In the present study, the relationship between SERPINA3 and other previously verified proliferation‐related molecules, including MCM6, 16 IGFBP2 , 15 and FKBP10 18 was evaluated. A strong correlation between the expression of SERPINA3 and these molecules in glioma suggests that SERPINA3 may participate in the proliferation of glioma cells.…”

“…For the same cases, we previously reported high expression of IDH1 mutation, 17 MCM6 protein, 16 FKBP10 protein, 18 and IGFBP2 mRNA 15 . Here, we simultaneously analyzed the relationship between SERPINA3 expression and the alterations biomarkers.…”

Annotation of pituitary neuroendocrine tumors with genome-wide expression analysis

“…A prognostic role has also been reported for some of these genes, both negative ( ERRFI1 ) [ 25 ], and positive ( SLC44A3 ) [ 29 ]. Additionally, several of the differentially expressed genes are proposed to be potential therapeutic targets, such as FAIM2 in small cell lung carcinoma [ 18 ], ERRFI1 in pancreatic carcinoma [ 25 ], RASA4 in triple-negative breast carcinoma [ 53 ], FKBP10 in gliomas [ 7 , 18 ], metastatic gastric carcinoma [ 16 ] and lung carcinoma [ 38 ], and CACNA2D in prostate carcinoma [ 18 ]. Overview of the most interesting genes differentially expressed between the cell-lineage based groups of PitNETs has been presented in Table 2 .…”