Exploration of Potential Targets and Mechanisms of Fisetin in the Treatment of Non-Small-Cell Lung Carcinoma via Network Pharmacology and In Vitro Validation

Ling, Junjun; Wang, Yuhong; Ma, Lihai; Chang, Aoshuang; Meng, Lingzhan; Zhang, Liang

doi:10.1155/2022/2383527

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…The protein expression of the three top genes was detected by western blot assay as previously described 18 . In brief, cells were harvested, washed with ice‐cold PBS, and lysed with RIPA buffer supplemented with protease inhibitor.…”

Section: Methodsmentioning

confidence: 99%

“…After intervention for 24 h, the mRNAs of the key genes were detected by RT-PCR assay as described previously. 18 Each sample was repeated in triplicate. GAPDH was used as the internal reference.…”

Section: The Expression Of the Key Gene In Hnc Cellsmentioning

confidence: 99%

“…The protein expression of the three top genes was detected by western blot assay as previously described. 18 In brief, cells were harvested, washed with ice-cold PBS, and lysed with RIPA buffer supplemented with protease inhibitor. Proteins were running on a 10% SDS-polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride membranes (Roche).…”

Section: Gapdh: (F: Attccacccatggcaaattc R: Gcatcgccccacttgatt)mentioning

confidence: 99%

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SPP1 as a key gene in the lymph node metastasis and a potential predictor of poor prognosis in head and neck carcinoma

Feng

Yuan

Sun

et al. 2022

J Oral Pathology Medicine

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Background: Lymph node metastasis (LNM) is an important cause leading to recurrence and development of head and neck carcinoma (HNC), with the precise mechanisms unclear. Thus, we aimed to identify the key genes involved in LNM and further evaluate their expressions and roles.Methods: A cohort of HNC in the TCGA was analyzed. The study involved three phases (one screening and two validation phases). First, the differentially expressed genes regarding LNM were screened, from which a key gene was identified by a series of data mining approaches. Then, the expressions and roles of the key gene were validated in HNC through bioinformatics. Afterward, the expression of the key gene was detected by qPCR, western blot, and Immunohistochemistry based on a cell model and a tissue microarray. Further, colony formation and transwell migration and invasion assays were used to evaluate the roles of the key gene.Results: SPP1 was overexpressed in HNC tissues and was identified as the key gene.Overexpression of SPP1 in HNC was correlated with advanced pathological stages and T-stage, as well as the presence of LNM, which predicted poor prognosis. The expression of SPP1 was closely associated with the infiltration of immune cells in HNC, especially M2 macrophages. Lab experiments confirmed that SPP1 silence in HNC cells resulted in weakened invasive and metastatic abilities. Conclusion:This study reveals that SPP1 may be a key gene associated with LNM in HNC, raising the possibility of SPP1 as a target for HNC prevention and treatment.

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Section: Methodsmentioning

confidence: 99%

Section: The Expression Of the Key Gene In Hnc Cellsmentioning

confidence: 99%

Section: Gapdh: (F: Attccacccatggcaaattc R: Gcatcgccccacttgatt)mentioning

confidence: 99%

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SPP1 as a key gene in the lymph node metastasis and a potential predictor of poor prognosis in head and neck carcinoma

Feng

Yuan

Sun

et al. 2022

J Oral Pathology Medicine

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“…After intervention for 24 h, the mRNAs of the top hub genes (TNF, VEGFA, IL6) were detected by RT-PCR assay as described previously ( Ling et al, 2022 ). Each sample was repeated in triplicate.…”

Section: Methodsmentioning

confidence: 99%

“…The protein expression of the three top genes was detected by western blot assay as previously described ( Ling et al, 2022 ). In brief, cells were harvested, washed with ice-cold PBS, and lysed with RIPA buffer supplemented with protease inhibitors.…”

Section: Methodsmentioning

confidence: 99%

Exploration of the effect of Celastrol on protein targets in nasopharyngeal carcinoma: Network pharmacology, molecular docking and experimental evaluations

et al. 2022

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Background: Celastrol, an important extract of Tripterygium wilfordii, shows strong antitumor activity in a variety of tumors including nasopharyngeal carcinoma (NPC). However, little is known about its targets in NPC. We aimed to screen the key gene targets of Celastrol in the treatment of NPC by means of in silico analyses (including network pharmacology and molecular docking) and experimental evaluations.Methods: The main target genes of Celastrol and the genes related to NPC were obtained by retrieving the relevant biological databases, and the common targets were screened. Protein-protein interaction analysis was used to screen the hub genes. Then, a “compound-target-disease” network model was created and molecular docking was used to predict the binding of Celastrol to the candidate hub proteins. Afterward, the expression changes of the candidate genes under the administration of Celastrol were verified in vitro and in vivo.Results: Sixty genes common to Celastrol and NPC were screened out, which may be related to numerous biological processes such as cell proliferation, apoptosis, and tube development, and enriched in various pathways such as PI3K- Akt, EGFR tyrosine kinase inhibitor resistance, and Apoptosis. The tight binding ability of the candidate hub proteins (TNF, VEGFA, and IL6) to Celastrol was predicted by molecular docking [Docking energy: TNF, −6.08; VEGFA,−6.76; IL6,−6.91(kcal/mol)]. In vitro experiments showed that the expression of TNF and VEGFA decreased while the expression of IL6 increased in NPC cells (CNE2 and HONE1) treated with Celastrol. In vivo experiments suggested that Celastrol significantly reduced the weight and volume of the transplanted tumors in tumor-bearing mice in vivo. The expression of TNF, VEGFA, and IL6 in the transplanted tumor cells could be regulated by using Celastrol, and the expression trends were consistent with the in vitro model.Conclusion: Several gene targets have been filtered out as the core targets of Celastrol in the treatment of NPC, which might be involved in a variety of signaling pathways. Hence, Celastrol may exert its anti-NPC activity through multiple targets and multiple pathways, which will provide new clues for further research. Future experiments are warranted to validate the findings.

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MYO1B as a prognostic biomarker and a therapeutic target in Arecoline‐associated oral carcinoma

Sun

Guo

Chen

et al. 2023

Molecular Carcinogenesis

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Background Arecoline, the main component of betel nut, induces malignant transformation of oral cells through complicated unclear mechanisms. Thus, we aimed to screen the key genes involved in Arecoline‐induced oral cancer and further verify their expressions and roles. Methods This study included a data‐mining part, a bioinformatics verification part, and an experimental verification one. First, the key gene related to oral cancer induced by Arecoline was screened. Then, the expression and clinical significance of the key gene in head and neck/oral cancer tissues were verified, and its downstream mechanisms of action were explored. Afterwards, the expression and roles of the key gene were verified by experiments at the histological and cytological levels. Results MYO1B was identified as the key gene. Overexpression of MYO1B was associated with lymph node metastasis and unfavorable outcomes in oral cancer. MYO1B may be mainly related to metastasis, angiogenesis, hypoxia, and differentiation. A positive correlation between MYO1B and the infiltration of macrophages, B cells, and dendritic cells was presented. MYO1B might have a close relationship with SMAD3, which may be enriched in the Wnt signaling pathway. MYO1B suppression markedly inhibited the proliferation, invasion, and metastasis abilities of both Arecoline‐transformed oral cells and oral cancer cells. Conclusion This study revealed MYO1B as a key gene in Arecoline‐induced oral tumorigenesis. MYO1B might be a novel prognostic indicator and therapeutic target for oral cancer.

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Exploration of Potential Targets and Mechanisms of Fisetin in the Treatment of Non-Small-Cell Lung Carcinoma via Network Pharmacology and In Vitro Validation

Cited by 7 publications

References 30 publications

SPP1 as a key gene in the lymph node metastasis and a potential predictor of poor prognosis in head and neck carcinoma

SPP1 as a key gene in the lymph node metastasis and a potential predictor of poor prognosis in head and neck carcinoma

Exploration of the effect of Celastrol on protein targets in nasopharyngeal carcinoma: Network pharmacology, molecular docking and experimental evaluations

MYO1B as a prognostic biomarker and a therapeutic target in Arecoline‐associated oral carcinoma

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