The SARS-CoV-2 Virus could Downregulate Dual Specificity Phosphatase-1 Expression in Oral Cancer: A Plausible Hypothesis that could Explain Oral Cancer Progression in the COVID-19 Pandemic and Post-pandemic Situation

Rajeswari Ramesh¹, Pearlcid Siroraj², Saranya Varadarajan³, Thodur Madapusi Balaji⁴, Shankargouda Patil⁵

¹Department of Oral and Maxillofacial Pathology, Siroraj Hospital, Thoothukudi, Tamil Nadu, India

²Department of Oral and Maxillofacial Surgery, Faculty of Dental Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India

³Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai, Tamil Nadu, India

⁴Tagore Dental College and Hospital, Chennai, Tamil Nadu, India

⁵Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, Jazan University, Jazan, Saudi Arabia

Corresponding Author: Shankargouda Patil, Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, Jazan University, Jazan, Saudi Arabia, Phone: +96 6507633755, e-mail: dr.ravipatil@gmail.com

How to cite this article: Ramesh R, Siroraj P, Varadarajan S, et al. The SARS-CoV-2 Virus could Downregulate Dual Specificity Phosphatase-1 Expression in Oral Cancer: A Plausible Hypothesis that could Explain Oral Cancer Progression in the COVID-19 Pandemic and Post-pandemic Situation. J Contemp Dent Pract 2022;23(10):963–964.

Source of support: Nil

Conflict of interest: None

ABSTRACT

This study explores the downregulation of Dual Specificity Phosphatase-1 (DUSP-1) expression in oral cancer progression during the pandemic and post-pandemic situations.

Keywords: COVID-19, Dual specificity phosphatase-1, Oral cancer, SARS-CoV-2.

The SARS-CoV-2 virus has been implicated as the causative organism for the COVID-19 illness that has been doing the rounds affecting the entire human rac.¹ This disease was upgraded as a pandemic by the World Health Organization in 2020.² Ever since then, many preventive measures such as the imposition of lockdowns, social distancing protocols, wearing of masks, and vaccination procedures have been devised and implemented at a global level to prevent the spread of the disease. It is known that the COVID-19 illness predominantly spreads through droplet infection and causes severe respiratory distress and pneumonia in some afflicted individuals requiring hospitalization and respiratory support.³

It is noteworthy that the SARS-CoV-2 virus enters the human system through certain portals, of which the oral cavity is significant.¹ The expression of ACE-2, the receptor for SARS-CoV-2 virus spike glycoprotein has been demonstrated in the oral cavity.⁴ Moreover, there is also evidence linking oral diseases such as oral cancer and periodontal disease to increased risk of viral entry through various molecular mechanisms.⁵ About oral cancer, it has been suggested that upregulation of certain mediators such as furin, cathepsin,⁵ and EMMPRIN⁶ make cancerous tissues more vulnerable to SARS-CoV-2 entry. In this connection, we suggest the importance and possible role that could be played by DUSP-1 that has not previously been explored.

Dual Specificity Phosphatase-1, also called MAPK phosphatase-1 (MKP-1), is an endogenous inhibitor of the MAPK pathway and affords anti-inflammatory effects by dephosphorylating of p38 MAPKs, switching off the pathway.⁷ This in turn has several effects such as inhibition of inflammation, anaphylaxis, and tissue destruction.⁸ It is noteworthy that DUSP-1 expression is downregulated in cancer progression as demonstrated in animal and human models.^9,10 Interestingly, the recent research has also shown that the SARS-CoV-2 virus could also attenuate DUSP-1 expression.¹¹ Vital data from an in silico, nasopharyngeal swab, and culture-based study from human subjects have demonstrated the inhibitory effect of the SARS-CoV-2 virus on DUSP-1 expression.¹¹ In the oral cancer scenario, this finding could have several implications as we list hereafter.

It is already proposed that oral cancer patients could be at increased risk for SARS-CoV-2 based on the overexpression of certain markers as previously explained. Now comes a situation where, after the SARS-CoV-2 infection, there could be increased rates of oral cancer progression in the COVID-19 affected patients mediated through DUSP-1 downregulation caused by the SARS-CoV-2 virus. This finding if proven would have large implications in understanding the progression of oral cancer in the current scenario. We have previously demonstrated the implications of lockdown protocols on cancer patient inflow rates in a tertiary cancer care center in India.¹² We at this point reiterate that the SARS-CoV-2 infection has caused multiple impacts which have still not been researched and explored. These impacts could have profound disastrous effects even after the pandemic situation ends. We suggest that clinical studies to understand oral cancer progression in the pandemic situation in SARS-CoV-2 affected oral cancer patients are required to understand if the deadly virus has enhanced cancer progression through molecular mechanisms such as DUSP-1 inhibition. If fruitful results are obtained from such clinical studies, it should become a clinical mandate to recall and review all cancer patients for progression and metastasis in the post-pandemic situation considering that many cancer patients could have been affected by both symptomatic and asymptomatic forms of SARS-CoV-2 infection and would have been unable to visit hospitals during the lockdown period.

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