Research Papers:

JunD accentuates arecoline-induced disruption of tight junctions and promotes epithelial-to-mesenchymal transition by association with NEAT1 lncRNA

Subarna Ghosh, Priyanka Dey Talukdar, Abhinandan Bhattacharjee, Sarbani Giri, Nitai Pada Bhattacharyya and Urmi Chatterji _

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Oncotarget. 2021; 12:1520-1539. https://doi.org/10.18632/oncotarget.28026

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Subarna Ghosh1, Priyanka Dey Talukdar1, Abhinandan Bhattacharjee2, Sarbani Giri3, Nitai Pada Bhattacharyya4 and Urmi Chatterji1,5

1 Cancer Research Laboratory, Department of Zoology, University of Calcutta, Kolkata 700019, West Bengal, India

2 Department of Otorhinolaryngology, Silchar Medical College, Silchar 788015, Assam, India

3 Department of Life Sciences, Assam University, Silchar 788011, Assam, India

4 Former Professor, Saha Institute of Nuclear Physics, Kolkata 700064, West Bengal, India

5 Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata 700098, West Bengal, India

Correspondence to:

Urmi Chatterji,email: [email protected]

Keywords: arecoline; tight junction; head and neck cancer; lncRNA-NEAT1; JunD

Received: January 07, 2021     Accepted: June 11, 2021     Published: July 20, 2021

Copyright: © 2021 Ghosh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Head and neck cancers are highly prevalent in south-east Asia, primarily due to betel nut chewing. Arecoline, the primary alkaloid is highly carcinogenic; however its role in promoting tumorigenesis by disrupting junctional complexes and increasing risk of metastasis is not well delineated. Subsequently, the effects of low and high concentrations of arecoline on the stability of tight junctions and EMT induction were studied. A microarray analysis confirmed involvement of a MAPK component, JunD, in regulating tight junction-associated genes, specifically ZO-1. Results established that although arecoline-induced phosphorylation of JunD downregulated expression of ZO-1, JunD itself was modulated by the lncRNA-NEAT1 in presence of arecoline. Increased NEAT1 in tissues of HNSCC patients significantly correlated with poor disease prognosis. Here we show that NEAT1-JunD complex interacted with ZO-1 promoter in the nuclear compartment, downregulated expression of ZO-1 and destabilized tight junction assembly. Consequently, silencing NEAT1 in arecoline-exposed cells not only downregulated the expression of JunD and stabilized expression of ZO-1, but also reduced expression of the EMT markers, Slug and Snail, indicating its direct regulatory role in arecoline-mediated TJ disruption and disease progression.

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