Multi-Omics Analysis to Characterize Cigarette Smoke Induced Molecular Alterations in Esophageal Cells

Khan, Aafaque Ahmad; Patel, Krishna; Patil, Shankargouda; Babu, Niraj; Mangalaparthi, Kiran K.; Solanki, Hitendra S.; Nanjappa, Vishalakshi; Kumari, Anjali; Manoharan, Malini; Coral, Karunakaran; Murugan, Saktivel; Nair, Bipin; Kumar, Rekha V.; Biswas, Manjusha; Sidransky, David; Gupta, Ravi; Gupta, Rohit; Khanna-Gupta, Arati; Kumar, Prashant; Chatterjee, Aditi; Gowda, Harsha

doi:10.3389/fonc.2020.01666

Cited by 2 publications

(2 citation statements)

References 68 publications

(75 reference statements)

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“…Protein estimation was done using the BCA assay using BSA as standard (Pierce, Waltham, MA) and then confirmed by visualization on SDS‐PAGE. In‐solution digestion was performed as previously described 24,25 . The 100 μg of protein was reduced using 10 mM dithiothreitol (DTT) at 60°C for 20 min, reduced proteins were then alkylated using 20 mM iodoacetamide (IAA) in dark at room temperature for 10 min.…”

Section: Methodsmentioning

confidence: 99%

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The unique molecular targets associated antioxidant and antifibrotic activity of curcumin in in vitro model of acute lung injury: A proteomic approach

et al. 2021

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Bleomycin (BLM) injury is associated with the severity of acute lung injury (ALI) leading to fibrosis, a high‐morbidity, and high‐mortality respiratory disease of unknown etiology. BLM‐induced ALI is marked by the activation of a potent fibrogenic cytokine transcription growth factor beta‐1 (TGFβ‐1), which is considered a critical cytokine in the progression of alveolar injury. Previously, our work demonstrated that a diet‐derived compound curcumin (diferuloylmethane), represents its antioxidative and antifibrotic application in TGF‐β1‐mediated BLM‐induced alveolar basal epithelial cells. However, curcumin‐specific protein targets, as well as its mechanism using mass spectrometry‐based proteomic approach, remain elusive. To elucidate the underlying mechanism, a quantitative proteomics approach and bioinformatics analysis were employed to identify the protein targets of curcumin in BLM or TGF‐β1‐treated cells. With subsequent in vitro experiments, curcumin‐related pathways and cellular processes were predicted and validated. The current study discusses two separate proteomics experiments using BLM and TGF‐β1‐treated cells with the proteomics approach, various unique target proteins were identified, and proteomic analysis revealed that curcumin reversed the expressions of unique proteins like DNA topoisomerase 2‐alpha (TOP2A), kinesin‐like protein (KIF11), centromere protein F (CENPF), and so on BLM or TGF‐β1 injury. For the first time, the current study reveals that curcumin restores TGF‐β1 induced peroxisomes like PEX‐13, PEX‐14, PEX‐19, and ACOX1. This was verified by subsequent in vitro assays. This study generated molecular evidence to deepen our understanding of the therapeutic role of curcumin at the proteomic level and may be useful to identify molecular targets for future drug discovery.

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Section: Methodsmentioning

confidence: 99%

“…Peptide estimation was done using Thermos Scientific™ Pierce™ quantitative colorimetric peptide assay#23275 to take an equal amount of peptides across the samples for mass spectrometry (MS) analysis. The dried peptides were cleaned using the C18 Stage Tip‐based method as described previously 24,25 …”

Section: Methodsmentioning

confidence: 99%

The unique molecular targets associated antioxidant and antifibrotic activity of curcumin in in vitro model of acute lung injury: A proteomic approach

et al. 2021

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Mediator complex subunit 1 promotes oral squamous cell carcinoma progression by activating MMP9 transcription and suppressing CD8+ T cell antitumor immunity

Li,

Sun,

Yang

et al. 2024

J Exp Clin Cancer Res

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Background The role of Mediator complex subunit 1 (MED1), a pivotal transcriptional coactivator implicated in diverse biological pathways, remains unexplored in the context of oral squamous cell carcinoma (OSCC). This study aims to elucidate the contributory mechanisms and potential impact of MED1 on the progression of OSCC. Methods The expression and clinical significance of MED1 in OSCC tissues were evaluated through the bioinformatics analyses. The effects of MED1 on the biological behavior of OSCC cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) assay, bioinformatic analysis, CD8+ T cell isolation experiment, coculture experiment, enzyme-linked immunosorbent assay (ELISA), and flow cytometric analysis were employed to elucidate the underlying mechanism through which MED1 operates in the progression of OSCC. Results MED1 exhibited upregulation in both OSCC tissues and multiple OSCC cell lines, which correlated with decreased overall survival in patients. In vitro experiments demonstrated that knockdown of MED1 in metastatic OSCC cell lines SCC-9 and UPCI-SCC-154 hindered cell migration and invasion, while overexpression of MED1 promoted these processes. Whereas, MED1 knockdown had no impact on proliferation of cell lines mentioned above. In vivo studies further revealed that downregulation of MED1 effectively suppressed distant metastasis in OSCC. Mechanistically, MED1 enhanced the binding of transcription factors c-Jun and c-Fos to the matrix metalloprotein 9 (MMP9) promoters, resulting in a significant upregulation of MMP9 transcription. This process contributes to the migration and invasion of SCC-9 and UPCI-SCC-154 cells. Furthermore, MED1 modulated the expression of programmed death-ligand 1 (PD-L1) through the Notch signaling pathway, consequently impacting the tumor-killing capacity of CD8+ T cells in the tumor microenvironment. Conclusions Our findings indicate that MED1 plays a pivotal role in OSCC progression through the activation of MMP9 transcription and suppression of CD8+ T cell antitumor immunity, suggesting that MED1 may serve as a novel prognostic marker and therapeutic target in OSCC.

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Multi-Omics Analysis to Characterize Cigarette Smoke Induced Molecular Alterations in Esophageal Cells

Cited by 2 publications

References 68 publications

The unique molecular targets associated antioxidant and antifibrotic activity of curcumin in in vitro model of acute lung injury: A proteomic approach

The unique molecular targets associated antioxidant and antifibrotic activity of curcumin in in vitro model of acute lung injury: A proteomic approach

Mediator complex subunit 1 promotes oral squamous cell carcinoma progression by activating MMP9 transcription and suppressing CD8+ T cell antitumor immunity

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