FKBP10 functioned as a cancer‐promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma

Wang, Ruogu; Zhang, Dan; Zhao, Chen; Wang, Qi‐Long; Qü, Hui; He, Qin

doi:10.1002/kjm2.12174

Cited by 19 publications

(14 citation statements)

References 19 publications

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“…Studies of various antitumor drugs have revealed that the inhibition of the PI3K/ Akt signaling pathway activation can induce cell-cycle arrest and apoptosis of tumors, thereby achieving effects of tumor suppression [23]. In gastric cancer, FKBP10 promotes the PI3K/AKT signaling pathway to affect the cell viability, colony-forming ability, migration, and invasive potential of gastric cancer cells [13]. In this study, we found that FKBP10 could promote cell proliferation by affecting the protein expression of c-Myc and cyclin D1 (cell cycle-related genes of PI3K/AKT pathway downstream) in cells.…”

Section: Discussionmentioning

confidence: 99%

“…e FKBP10 gene, a member of FK506-binding family, is located at 17q21.2 and encodes a protein with a molecular weight of 65 kDa. FK506-binding proteins (FKBPs) are named for their ability to specifically bind the immunosuppressant FK506 (tacrolimus) [12,13]. Specifically, FKBPs bind to the FK506 to significantly inhibit the activity of peptidyl-prolyl cis/trans isomerase (PPIase) domain activity, thereby preventing Ca2+-dependent associated pathway activation [14].…”

Section: Introductionmentioning

confidence: 99%

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A Novel Biomarker, FKBP10, for Poor Prognosis Prediction in Patients with Clear Cell Renal Cell Carcinoma

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To screen genes associated with poor prognosis of clear cell renal cell carcinoma (CcRCC) from the public databases HPA (Human Protein Atlas), UALCAN, and GEPIA (Gene Expression Profiling Interactive Analysis) and to investigate the expression of FKBP10 in CcRCC and the effect on prognosis of the patients and the biological behavior of CcRCC cells. Methods. The tumor tissues and adjacent noncancerous tissues of 42 patients with CcRCC diagnosed and treated in our hospital were collected, and the general information of the patients was recorded. FKBP10 expression in the tissues was determined by qRT-PCR and western blot, and its relationship with general information and prognosis of patients was analyzed. Knockdown or overexpression experiments were carried out with the human proximal tubule epithelial cell line HK-2 and CcRCC cell lines Caki-1, 786-O, ACHN, and A498 to verify the relationship between FKBP10 expression and cell proliferation and adhesion ability using MTT assay and fibronectin adhesion assay, respectively. Western blot was utilized to examine the protein expression level of c-Myc, cyclin D1, and Bcl-2 in the cells. Results. FKBP10 was highly expressed in CcRCC tissues and cells and was correlated with poor prognosis. In addition, FKBP10 expression was positively correlated with CcRCC tumor size and staging and negatively correlated with tumor differentiation. Moreover, knockdown of FKBP10 significantly inhibited the proliferation of CcRCC cells, notably declined the protein expression of c-Myc, cyclin D1, and Bcl-2, and promoted cell adhesion. Conclusion. FKBP10 is highly expressed in CcRCC tissues and cells and is associated with poor prognosis in patients. FKBP10 participated in the occurrence and development of CcRCC by promoting cell proliferation and inhibiting apoptosis and adhesion.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Biomarker, FKBP10, for Poor Prognosis Prediction in Patients with Clear Cell Renal Cell Carcinoma

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…The decrease in FKBP8 expression can induce apoptosis through the regulation of Bcl-2 (25)(26)(27). FKBP10 mediates aggressive phenotypes of stomach adenocarcinoma by regulating the PI3K signaling pathway (28). These studies demonstrate that FKBP genes play pivotal roles in tumorigenesis; however, there is currently no study of FKBPs in ccRCC, which means that the value of the FKBP family for predicting prognosis of ccRCC is still unclear and remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Multi-Omics Analysis of the Expression and Prognosis for FKBP Gene Family in Renal Cancer

et al. 2021

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BackgroundThe FK506-binding protein (FKBP) is a family of intracellular receptors that can bind specifically to the immunosuppressant FK506 and rapamycin. Although FKBPs play crucial roles in biological processes and carcinogenesis, their prognostic value and molecular mechanism in clear cell renal cell carcinoma (ccRCC) remain unclear.MethodsUsing pan-cancer data from The Cancer Genome Atlas (TCGA) and public databases, we analyzed the expression and correlation of FKBPs in 33 tumor types. Survival and Cox regression analyses were employed to explore the prognostic value of FKBPs. The relationship with tumor microenvironment and stemness indices was taken into account to evaluate the function of FKBPs. We constructed a risk score model to predict the prognosis of patients with ccRCC. The receiver operating characteristic (ROC) curve was performed to further test the prognostic ability of our model. Nomogram, joint effects analysis, and clinical relevance were performed to assist the clinician. Gene set enrichment analysis (GSEA) and cell line experiments were performed to investigate the function and molecular mechanisms of FKBPs in patients with ccRCC. Paired clinical specimens and multi-omics analysis were used to further validate and explore the factors affecting gene expression in ccRCC patients.ResultsThe expression levels of FKBP10 and FKBP11 were higher in ccRCC tissues than in normal tissues. The alteration in expression may be because of the degree of DNA methylation. Increased expression levels of FKBP10 and FKBP11 were associated with worse overall survival (OS). More importantly, GSEA revealed that FKBP10 is mainly involved in cell metabolism and autophagy, whereas FKBP11 is mainly associated with immune-related biological processes and autophagy. Cell Counting Kit 8 (CCK-8) and Transwell assays revealed that knockdown of FKBP10 and FKBP11 inhibits proliferation, migration, and invasion of the ccRCC cell line.ConclusionFKBP10 and FKBP11 play important roles in ccRCC phenotypes and are potential prognostic markers as well as new therapeutic targets for patients with ccRCC.

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“…Thirteen of 55 PmBs (Table 2) were confirmed by the data of the literature to play certain roles in occurrence and development of GA and were biomarkers or potential therapeutic targets of GA. For example, GPRC5A and SOX9 have been shown to be related to occurrence and development of GA (Liu et al, 2016;, and their expression levels changed more than fourfold in the GA vs. adjacent control samples according to the result of DE RNA analysis (log 2 FC > 2). FCMET has been confirmed as a resistance factor in GA (Ebert et al, 2019), and Wang R. G. et al (2020) demonstrated that FKBP10 may be a crucial player mediating cell proliferation, invasion, and migration by regulating the PI3K signaling pathway in GA. Twenty-seven of 55 PmBs (Table 2) were shown to be associated with other cancers according to the data of the literature. Thus, mRBioM identified some new GA-related mRNAs.…”

Section: Discussionmentioning

confidence: 97%

mRBioM: An Algorithm for the Identification of Potential mRNA Biomarkers From Complete Transcriptomic Profiles of Gastric Adenocarcinoma

Dong

Rao

et al. 2021

Front. Genet.

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PurposeIn this work, an algorithm named mRBioM was developed for the identification of potential mRNA biomarkers (PmBs) from complete transcriptomic RNA profiles of gastric adenocarcinoma (GA).MethodsmRBioM initially extracts differentially expressed (DE) RNAs (mRNAs, miRNAs, and lncRNAs). Next, mRBioM calculates the total information amount of each DE mRNA based on the coexpression network, including three types of RNAs and the protein-protein interaction network encoded by DE mRNAs. Finally, PmBs were identified according to the variation trend of total information amount of all DE mRNAs. Four PmB-based classifiers without learning and with learning were designed to discriminate the sample types to confirm the reliability of PmBs identified by mRBioM. PmB-based survival analysis was performed. Finally, three other cancer datasets were used to confirm the generalization ability of mRBioM.ResultsmRBioM identified 55 PmBs (41 upregulated and 14 downregulated) related to GA. The list included thirteen PmBs that have been verified as biomarkers or potential therapeutic targets of gastric cancer, and some PmBs were newly identified. Most PmBs were primarily enriched in the pathways closely related to the occurrence and development of gastric cancer. Cancer-related factors without learning achieved sensitivity, specificity, and accuracy of 0.90, 1, and 0.90, respectively, in the classification of the GA and control samples. Average accuracy, sensitivity, and specificity of the three classifiers with machine learning ranged within 0.94–0.98, 0.94–0.97, and 0.97–1, respectively. The prognostic risk score model constructed by 4 PmBs was able to correctly and significantly (∗∗∗p < 0.001) classify 269 GA patients into the high-risk (n = 134) and low-risk (n = 135) groups. GA equivalent classification performance was achieved using the complete transcriptomic RNA profiles of colon adenocarcinoma, lung adenocarcinoma, and hepatocellular carcinoma using PmBs identified by mRBioM.ConclusionsGA-related PmBs have high specificity and sensitivity and strong prognostic risk prediction. MRBioM has also good generalization. These PmBs may have good application prospects for early diagnosis of GA and may help to elucidate the mechanism governing the occurrence and development of GA. Additionally, mRBioM is expected to be applied for the identification of other cancer-related biomarkers.

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FKBP10 functioned as a cancer‐promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma

Cited by 19 publications

References 19 publications

A Novel Biomarker, FKBP10, for Poor Prognosis Prediction in Patients with Clear Cell Renal Cell Carcinoma

A Novel Biomarker, FKBP10, for Poor Prognosis Prediction in Patients with Clear Cell Renal Cell Carcinoma

Multi-Omics Analysis of the Expression and Prognosis for FKBP Gene Family in Renal Cancer

mRBioM: An Algorithm for the Identification of Potential mRNA Biomarkers From Complete Transcriptomic Profiles of Gastric Adenocarcinoma

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