Alcohol drinking inhibits <scp>NOTCH</scp>–<scp>PAX9</scp> signaling in esophageal squamous epithelial cells

Shi, Menghan; Ren, Shuang; Chen, Hao; Li, Jing; Huang, Caizhi; Li, Yahui; Han, Yuning; Li, Yong; Sun, Zheng; Chen, Xiaoxin; Xiong, Zhaohui

doi:10.1002/path.5602

Cited by 8 publications

(3 citation statements)

References 58 publications

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“…IHC staining of tumor tissue was performed as previously described [ 31 ]. For IHC staining, deparaffinized sections were pretreated to retrieve antigens with a Tris-based Antigen Unmasking Solution (Vector Laboratories, Burlingame, CA, USA) before blocking with 10% normal serum and then applying either of the previously discussed antibodies and anti-PTK6 (Thermo Fisher Scientific) at 4 °C overnight.…”

Section: Methodsmentioning

confidence: 99%

Knockdown of microRNA-214-3p Promotes Tumor Growth and Epithelial-Mesenchymal Transition in Prostate Cancer

Cagle

Smith

Adekoya

et al. 2021

Cancers

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Abnormal expression of microRNA miR-214-3p (miR-214) is associated with multiple cancers. In this study, we assessed the effects of CRISPR/Cas9 mediated miR-214 depletion in prostate cancer (PCa) cells and the underlying mechanisms. Knockdown of miR-214 promoted PCa cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and increased resistance to anoikis, a key feature of PCa cells that undergo metastasis. The reintroduction of miR-214 in miR-214 knockdown cells reversed these effects and significantly suppressed cell proliferation, migration, and invasion. These in vitro studies are consistent with the role of miR-214 as a tumor suppressor. Moreover, miR-214 knockout increased tumor growth in PCa xenografts in nude mice supporting its anti-oncogenic role in PCa. Knockdown of miR-214 increased the expression of its target protein, Protein Tyrosine Kinase 6 (PTK6), a kinase shown to promote oncogenic signaling and tumorigenesis in PCa. In addition, miR-214 modulated EMT as exhibited by differential regulation of E-Cadherin, N-Cadherin, and Vimentin both in vitro and in vivo. RNA-seq analysis of miR-214 knockdown cells revealed altered gene expression related to PCa tumor growth pathways, including EMT and metastasis. Collectively, our findings reveal that miR-214 is a key regulator of PCa oncogenesis and is a potential novel therapeutic target for the treatment of the disease.

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Section: Methodsmentioning

confidence: 99%

Knockdown of microRNA-214-3p Promotes Tumor Growth and Epithelial-Mesenchymal Transition in Prostate Cancer

Cagle

Smith

Adekoya

et al. 2021

Cancers

Self Cite

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“…Direct exposure to alcohol has previously been shown to mediate an increase in epithelial cell proliferation and a decrease in differentiation (Liu et al, 2015; Shi et al, 2021). Chronic alcohol administration in rats results in an increase in esophageal epithelial proliferation that disappears with removal of the salivary glands, demonstrating both the importance of salivary glands for growth factor production and salivary gland associated acetaldehyde (Simanowski et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Direct and indirect effects of alcohol and its toxic metabolite acetaldehyde on human esophageal myofibroblasts and epithelial cells

Khalatbari

Castle

et al. 2023

Alcohol: Clinical and Experimental Research

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Background Mechanisms by which alcohol increases the risk of esophageal squamous cell carcinoma remain undefined. Human esophageal myofibroblasts (HEMFs) subjacent to the squamous epithelium are exposed directly to these agents via epithelial barrier defects and indirectly via factors derived from the exposed epithelium. Our aim was to investigate the cellular biology of HEMFs and HEMF‐esophageal epithelial cell interactions in response to alcohol and its toxic metabolite acetaldehyde. Methods An immortalized HEMF and a human esophageal epithelial cell line (Epi) were treated with alcohol (0 to 200 mM) or acetaldehyde (0 to 100 μM) in a cyclic fashion or incubated with supernatants collected from treated cells. Healthy cell %, reactive oxygen species (ROS), and proliferation were assessed via flow cytometry, luminescence, scratch wound, and colorimetric assays, respectively. A 15‐plex multiplex assay was performed on cell supernatants, followed by IL‐6 and IL‐8 qRT–PCR and ELISA. Results Healthy HEMF decreased to less than 80% at 30 mM alcohol and 70 μM acetaldehyde, with microscopic changes at 40 μM acetaldehyde. HEMF ROS was detected at 100 mM alcohol and 80 μM acetaldehyde. Supernatants from 30 mM alcohol‐ or 40 μM acetaldehyde‐treated HEMFs increased Epi proliferation more than two‐fold that of lower doses. In the complementary studies, healthy Epi cells decreased to less than 80% at 50 mM and 70 μM acetaldehyde, with microscopic changes at 40 μM. Supernatants from Epi treated with 50 mM alcohol or 40 μM acetaldehyde increased HEMF proliferation more than two‐fold that of lower doses. A multiplex assay of supernatants showed the greatest increase in concentrations of IL‐6 and IL‐8 in HEMFs and in Epi treated with higher doses of alcohol or acetaldehyde. Neutralization of IL‐6 and IL‐8 in supernatants of HEMFS and esophageal epithelial cells inhibited the proliferation of Epi and HEMFs, respectively. Conclusions Alcohol and acetaldehyde doses in which the majority of HEMFs and epithelial cells are healthy, elicit the production of paracrine mediators with pro‐proliferative effects on neighboring cells. Understanding the effect of alcohol and acetaldehyde on HEMFs and HEMF‐epithelial interactions could help to identify the molecular basis by which alcohol increases the risk for esophageal cancer.

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“…On the other hand, EMT is accompanied with the loss of epithelial cell junction proteins and gain of mesenchymal markers. The significant upregulation of epithelial marker: Cldn10 [ 42 ], Itgb4 [ 43 ], Pax9 [ 44 ], and Itga3 [ 45 ] may disturb the EMT process by promoting the MEPS epithelial cells proliferation, which may also be involve in this ceRNA regulatory network. Taking together, these may indicate that the LncRNA-NONMMUT100923.1 could regulate Cdsn expression by competitively binding to endogenous miR-200a-3p.…”

Section: Discussionmentioning

confidence: 99%

LncRNA-NONMMUT100923.1 regulates mouse embryonic palatal shelf adhesion by sponging miR-200a-3p to modulate medial epithelial cell desmosome junction during palatogenesis

Zhang

Zhou

et al. 2023

Heliyon

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Alcohol drinking inhibits NOTCH–PAX9 signaling in esophageal squamous epithelial cells

Cited by 8 publications

References 58 publications

Knockdown of microRNA-214-3p Promotes Tumor Growth and Epithelial-Mesenchymal Transition in Prostate Cancer

Knockdown of microRNA-214-3p Promotes Tumor Growth and Epithelial-Mesenchymal Transition in Prostate Cancer

Direct and indirect effects of alcohol and its toxic metabolite acetaldehyde on human esophageal myofibroblasts and epithelial cells

LncRNA-NONMMUT100923.1 regulates mouse embryonic palatal shelf adhesion by sponging miR-200a-3p to modulate medial epithelial cell desmosome junction during palatogenesis

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