Targeting STAT proteins via computational analysis in colorectal cancer

Context Cardamonin (CDN) can suppress cell growth in colorectal cancer (CRC), a common digestive malignancy. Objective We explored the effect and mechanism of CDN on metastatic CRC. Materials and methods Two cell lines (HT29 and HCT116) were initially treated with CDN at different concentrations (5, 10 and 20 μmol/L) or 50 μmol/L propranolol (positive control) for 24 or 48 h. Then, the two cell lines were separately transfected with siADRB2 and ADRB2 overexpression plasmids, and further treated with 10 μmol/L CDN for 24 h. The cell viability, migration and invasion were determined by cell counting kit-8 (CCK-8), wound healing and transwell assays, respectively. The levels of ADRB2, matrix metalloprotease (MMP)-2, MMP-9, E-cadherin and N-cadherin were measured by Western blotting or/and RT-qPCR. A CRC metastasis model was established to evaluate the antimetastatic potential of CDN (25 mg/kg). Results ADRB2 (3.2-fold change; p < 0.001) was highly expressed in CRC tissues. CDN at 10 μmol/L suppressed viability (69% and 70%), migration (33% and 66%), invasion (43% and 72%) and ADRB2 expression (2.2- and 2.84-fold change) in HT29 and HCT116 cells ( p < 0.001). CDN at 10 μmol/L inhibited MMP-2, MMP-9 and N-cadherin expression but promoted E-cadherin expression in CRC cells ( p < 0.001). Importantly, the effect of CDN on CRC cells was impaired by ADRB2 overexpression, but further enhanced by ADRB2 down-regulation ( p < 0.01). Additionally, ADRB2 overexpression reversed the inhibitory effect of CDN on metastatic lung nodules ( p < 0.05). Discussion and conclusions: CDN is a potential candidate for the treatment of metastatic CRC in clinical practice.

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“… 2020 ; Dariya et al. 2021 ). Thus, there is a possibility for the potential crosstalk between ADRB2 and STAT3 or miRNA in CRC.…”

Section: Discussionmentioning

confidence: 99%

Cardamonin suppressed the migration, invasion, epithelial mesenchymal transition (EMT) and lung metastasis of colorectal cancer cells by down-regulating ADRB2 expression

Zheng

Fan

2022

Pharmaceutical Biology

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Section: Discussionmentioning

confidence: 99%

“…Numerous studies have shown that different STAT family members play essential roles in the development of several cancers, including oral, 9 bladder, 10 cervical, 11 and colorectal cancers. 12 It has been proposed that the JAK/STAT signaling pathway is involved in the development of UCEC, and targeted inhibition of the IL‐6 receptor and its downstream effectors JAK1 and STAT3 significantly reduces UCEC tumor cell growth. 23 However, no bioinformatic analysis has been reported on the various STAT family members in endometrial cancer, and whether STAT family expression is associated with tumor immune infiltration in UCEC remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…IGF2BP3 promotes STAT proteins, which play an important role in cervical cancer development, and JAK/STAT pathway inhibition may be integral in promoting tumor cell death 11 . Colorectal cancer progression is caused by dysregulation of cytoplasmic transcription factors, including STAT proteins involved in the JAK/STAT signaling pathway 12 . However, the expression and prognosis of different STAT family members in endometrial cancer and their relationship with the level of immune infiltration in UCEC remain unknown.…”

Section: Introductionmentioning

confidence: 99%

“… 11 Colorectal cancer progression is caused by dysregulation of cytoplasmic transcription factors, including STAT proteins involved in the JAK/STAT signaling pathway. 12 However, the expression and prognosis of different STAT family members in endometrial cancer and their relationship with the level of immune infiltration in UCEC remain unknown. No studies have reported a bioinformatic analysis of the STAT family in endometrial cancer.…”

Section: Introductionmentioning

confidence: 99%

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Signal transducer and activator of transcription family is a prognostic marker associated with immune infiltration in endometrial cancer

Zhou

Dai

et al. 2022

Clinical Laboratory Analysis

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Background Signal transducer and activator of transcription (STAT) is a unique protein family that binds to DNA and plays a vital role in regulating major physiological cellular processes. Seven STAT genes have been identified in the human genome. Several studies suggest STAT family members to be involved in cancer development, progression, and metastasis. However, the predictive relationship between STAT family expression and immune cell infiltration in endometrial cancer remains unknown. Methods We explored STAT family expression and prognosis in endometrial cancer using various databases. The STRING, GeneMANIA, and DAVID databases, along with GO and KEGG analyses, were used to construct a protein interaction network of related genes. Finally, the TIMER database and ssGSEA immune infiltration algorithm were used to investigate the correlation of STAT family expression with the immune infiltration level in uterine corpus endometrial carcinoma (UCEC). Results Our study showed that different STAT family members are differentially expressed in UCEC. STAT1 and STAT2 expression increased at various stages of UCEC, and STAT5A, STAT5B, and STAT6 levels were decreased. STAT3 and STAT4 expression was not significantly different between UCEC and normal tissues. High STAT1 expression may be a prognostic disadvantage of UCEC, and high STAT6 expression may improve UCEC patient prognosis. The STAT family‐associated genes were significantly enriched in signal transduction, protein binding, DNA binding, and ATP binding upon GO analysis. Related genes in the KEGG analysis were mainly enriched in pathways in cancer, viral carcinogenesis, chemokine signaling pathway, JAK/STAT signaling pathway, and regulation of the actin cytoskeleton. In terms of immune infiltration, STAT1 and STAT2 were positively correlated with B, CD8+ T, CD4+ T, and dendritic cells, and neutrophils (p < 0.05). All STAT family members were positively correlated with neutrophils and dendritic cells (p < 0.05). STAT1 and STAT2 showed similar correlations with all immune cell types, whereas STAT1 and STAT6 showed opposite correlations. Conclusion These findings suggest that the STAT family is a prognostic marker, and the immune infiltration level, a therapeutic target, for endometrial cancer.

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Expanding CYLD protein in NF-κβ/TNF-α signaling pathway in response to Lactobacillus acidophilus in non-metastatic rectal cancer patients

Zamani,

Khalighfard,

Kalhori

et al. 2023

Med Oncol

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Introduction:CYLD gene is a tumor suppressor, reducing in many cancers. Here, we aimed to investigate CYLD protein level and NF-κβ/TNF-α signaling pathway in rectal cancer patients with Lactobacillus acidophilus (L. acidophilus) consumption. Methods:One hundred ten patients with non-metastatic rectal cancer were randomly divided into L. acidophilus probiotic (500 mg, three times daily) and placebo groups for 13 weeks. The expression of CYLD, TNF-α, and NF-κB proteins and the genes involved in the NF-κβ/TNF-α pathway were evaluated using ELISA and qPCR techniques.The survival rate was measured after ve years. Results:Unlike the placebo group, the results showed a signi cant increase in the expression of CYLD protein and tumor suppressor genes, including FOXP3, ROR-γ, Caspase3, GATA3, T-bet, and a considerable decrease in the expression of NF-ҝβ and TNF-α proteins and oncogenes, including STAT3, 4, 5, 6, and SMAD 3, in the probiotic group. A higher overall survival rate was seen after L. acidophilus consumption compared to the placebo group (P < 0.05). Conclusion:L. acidophilus consumption can reduce in ammation factors by affecting CYLD protein and its downstream signaling pathways.

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Targeting STAT proteins via computational analysis in colorectal cancer

Cited by 18 publications

References 47 publications

Cardamonin suppressed the migration, invasion, epithelial mesenchymal transition (EMT) and lung metastasis of colorectal cancer cells by down-regulating ADRB2 expression

Cardamonin suppressed the migration, invasion, epithelial mesenchymal transition (EMT) and lung metastasis of colorectal cancer cells by down-regulating ADRB2 expression

Signal transducer and activator of transcription family is a prognostic marker associated with immune infiltration in endometrial cancer

Expanding CYLD protein in NF-κβ/TNF-α signaling pathway in response to Lactobacillus acidophilus in non-metastatic rectal cancer patients

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