Tissue Profile of CDK4 and STAT3 as Possible Innovative Therapeutic Targets in Urinary Bladder Cancer

Aboushousha, Tarek; Hammam, Olfat; Aref, Ahmed; Kamel, Amira; Badawy, Mohamed; Hamid, Arif

doi:10.31557/apjcp.2020.21.2.547

Cited by 17 publications

(11 citation statements)

References 28 publications

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“…CDK4/6 bind to cyclin D to form a kinase-active complex, which phosphorylates retinoblastoma protein and drives the progression from G1 to S phase (27). Several studies have demonstrated that CDK4 is upregulated in cancer (28)(29)(30)(31)(32)(33) and inhibiting CDK4 expression increases the efficacy of clinical treatments for breast cancer, melanoma, liposarcoma, and mantle cell lymphoma (34)(35)(36)(37). This indicates that CDK4 could be a target for the treatment of malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

Coiled-Coil Domain-Containing 68 Downregulation Promotes Colorectal Cancer Cell Growth by Inhibiting ITCH-Mediated CDK4 Degradation

Jiao

et al. 2021

Front. Oncol.

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Coiled-coil domain-containing 68 (CCDC68) plays different roles in cancer and is predicted as a tumor suppressor in human colorectal cancer (CRC). However, the specific role of CCDC68 in CRC and the underlying mechanisms remain unknown. Here, we showed that CCDC68 expression was lower in CRC than that in corresponding normal tissues, and CCDC68 level was positively correlated with disease-free survival. Ectopic expression of CCDC68 decreased CRC cell proliferation in vitro and suppressed the growth of CRC xenograft tumors in vivo. CCDC68 caused G0/G1 cell cycle arrest, downregulated CDK4, and upregulated ITCH, the E3 ubiquitin ligase responsible for CDK4 protein degradation. This increased CDK4 degradation, which decreased CDK4 protein levels and inhibited CRC tumor growth. Collectively, the present results identify a novel CDK4 regulatory axis consisting of CCDC68 and ITCH, which suggest that CCDC68 is a promising target for the treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

Coiled-Coil Domain-Containing 68 Downregulation Promotes Colorectal Cancer Cell Growth by Inhibiting ITCH-Mediated CDK4 Degradation

Jiao

et al. 2021

Front. Oncol.

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“…To investigate how PRDX6 regulated cell proliferation signaling, the GSEA analysis and found JAK-STAT3 pathway was significantly enriched in PRDX high group (Figure 6E, Figure 8A). STAT3 plays as an important role in urological related tumors 34 , and previous study has confirmed that STAT3 as the upstream signaling of CDK4/6 pathway 35 . Taken together, we speculated that JAK-STAT3 signaling can be regulated by PRDX6 to impact the proliferation of BLCA cells.…”

Section: Prdx6 Promotes Bladder Cancer Cell Proliferation Via Jak2-stmentioning

confidence: 73%

Integrative Analysis the characterization of peroxiredoxins in pan-cancer

Gao

Meng

Yue

et al. 2020

Preprint

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Peroxiredoxins (PRDXs) are antioxidant enzymes protein family members that involves the process of several biological functions, such as differentiation, cell growth. Considerable evidence demonstrates that PRDXs play critical roles in the occurrence and development of carcinomas. However, a systematic analysis of PRDXs in cancers is deficiency. Therefore, we perform a comprehensive analysis of PRDXs in 33 cancer types including mRNA expression profiles, genetic alterations, methylation, prognostic values, potential biological pathways and target drugs. Moreover, we validated that PRDX6 could regulate cancer cell proliferation via JAK2-STAT3 pathway and involve into the process of cell cycle in bladder cancer.

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“…8 A). STAT3 plays as an important role in urological related tumors [ 37 ], and previous study has confirmed that STAT3 as the upstream signaling of CDK4/6 pathway [ 38 ]. Taken together, we speculated that PRDX6 modulates JAK-STAT3 signaling thus regulating proliferation of BLCA cells.…”

Section: Resultsmentioning

confidence: 99%

Integrative analysis the characterization of peroxiredoxins in pan-cancer

et al. 2021

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Background Peroxiredoxins (PRDXs) are an antioxidant enzymes protein family involved in several biological functions such as differentiation, cell growth. In addition, previous studies report that PRDXs play critical roles in the occurrence and development of carcinomas. However, few studies have conducted systematic analysis of PRDXs in cancers. Therefore, the present study sought to explore the molecular characteristics and potential clinical significance of PRDX family members in pan cancer and further validate the function of PRDX6 in bladder urothelial carcinoma (BLCA). Methods A comprehensive analysis of PRDXs in 33 types of cancer was performed based on the TCGA database. This involved an analysis of mRNA expression profiles, genetic alterations, methylation, prognostic values, potential biological pathways and target drugs. Moreover, both the gain and loss of function strategies were used to assess the importance and mechanism of PRDX6 in the cell cycle of BLCA. Result Analysis showed abnormal expression of PRDX1-6 in several types of cancer compared to normal tissues. Univariate Cox proportional hazard regression analysis showed that expression levels of PRDX1, PRDX4 and PRDX6 were mostly associated with poor survival of OS, DSS and PFI, and PRDX2 and PRDX3 with favorable survival. In addition, the expression of PRDX genes were positively correlated with CNV and negatively with methylation. Moreover, analysis based on PharmacoDB dataset showed that the augmented levels of PRDX1, PRDX3 and PRDX6 were significantly correlated with EGFR/VEGFR inhibitor drugs. Furthermore, knocking down of PRDX6 inhibited growth of cancer cells through the JAK2-STAT3 in bladder cell lines. Conclusions PRDXs are potential biomarkers and therapeutic targets for several carcinomas, especially for BLCA. In addition, PRDX6 could regulate proliferation of cancer cell via JAK2-STAT3 pathway and involve into the process of cell cycle in BLCA.

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Tissue Profile of CDK4 and STAT3 as Possible Innovative Therapeutic Targets in Urinary Bladder Cancer

Cited by 17 publications

References 28 publications

Coiled-Coil Domain-Containing 68 Downregulation Promotes Colorectal Cancer Cell Growth by Inhibiting ITCH-Mediated CDK4 Degradation

Coiled-Coil Domain-Containing 68 Downregulation Promotes Colorectal Cancer Cell Growth by Inhibiting ITCH-Mediated CDK4 Degradation

Integrative Analysis the characterization of peroxiredoxins in pan-cancer

Integrative analysis the characterization of peroxiredoxins in pan-cancer

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