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<p>Oral potentially malignant disorders (OPMDs) refer to any oral mucosal anomaly linked to a statistically significant risk of acquiring cancer. Oral squamous cell carcinoma (OSCC) accounts for over 90% of all oral cancers and is one of the most frequent malignancies globally. Ghrelin, a gastrointestinal peptide hormone comprising of 28 amino acids, endogenously binds with the growth hormone secretagogue receptor. The rationale is to explore expression and interaction of ghrelin and genes associated with OPMDs &amp; OSCC in oral carcinogenesis.The objective of this study is to access the interaction of ghrelin with mTOR, PI3K, AKT and NF-κB. and to investigate ghrelin levels in OPMDs and OSCC and molecular expression of mTOR, PI3K, AKT and NF-κB in OPMD and OSCC.Patch Dock, a geometry-based molecular docking algorithm, was used for docking the ghrelin with mTOR, PI3K, AKT, and NF-κB. The present investigation was held on patients (<i>n</i> = 60) who visited the Department of Oral medicine at Saveetha Dental College and Hospitals, Chennai. The sample was divided into three groups: group 1 comprises healthy individuals; group 2 were patients with OPMDs and group 3 consists of patients with OSCC.Ghrelin forms the 11 hydrogen bond and 176 non-bonded interactions with mTOR protein. PI3K also showed a strong interaction with ghrelin with 26 hydrogen bonds and 471 non–bonded interactions. AKT formed four hydrogen bonds and 322 non–bonded interactions with ghrelin protein. NF-κB also showed a strong binding with ghrelin with four hydrogen bond interactions and 167 non-bonded interactions Mean ± SD for healthy individuals is 0.855 ± 0.06. Mean ± SD for OPMD and OSCC are 1.252 ± 0.06 and 1.91 ± 0.03, respectively, which showed a significant difference between OPMD and OSCC compared to healthy individuals.The complex changes of oral malignant transformation were closely linked to ghrelin via mTOR, PI3K, AKT and NF-κB signaling pathways, thus indicating that ghrelin could be a potentially useful target to regulate the malignant transformation of OPMD.</p>

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Role of Ghrelin in the Development of Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma by Modulating the Expression of PI3K/Akt and mTOR/ NF-κB Signaling Molecules

  • 期刊论文

  • 发表日期：

    2025年12月6日

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  • Dinesh Yasothkumar,
  • Pratibha Ramani,
  • Selvaraj Jayaraman

摘要

Oral potentially malignant disorders (OPMDs) refer to any oral mucosal anomaly linked to a statistically significant risk of acquiring cancer. Oral squamous cell carcinoma (OSCC) accounts for over 90% of all oral cancers and is one of the most frequent malignancies globally. Ghrelin, a gastrointestinal peptide hormone comprising of 28 amino acids, endogenously binds with the growth hormone secretagogue receptor. The rationale is to explore expression and interaction of ghrelin and genes associated with OPMDs & OSCC in oral carcinogenesis.The objective of this study is to access the interaction of ghrelin with mTOR, PI3K, AKT and NF-κB. and to investigate ghrelin levels in OPMDs and OSCC and molecular expression of mTOR, PI3K, AKT and NF-κB in OPMD and OSCC.Patch Dock, a geometry-based molecular docking algorithm, was used for docking the ghrelin with mTOR, PI3K, AKT, and NF-κB. The present investigation was held on patients (n = 60) who visited the Department of Oral medicine at Saveetha Dental College and Hospitals, Chennai. The sample was divided into three groups: group 1 comprises healthy individuals; group 2 were patients with OPMDs and group 3 consists of patients with OSCC.Ghrelin forms the 11 hydrogen bond and 176 non-bonded interactions with mTOR protein. PI3K also showed a strong interaction with ghrelin with 26 hydrogen bonds and 471 non–bonded interactions. AKT formed four hydrogen bonds and 322 non–bonded interactions with ghrelin protein. NF-κB also showed a strong binding with ghrelin with four hydrogen bond interactions and 167 non-bonded interactions Mean ± SD for healthy individuals is 0.855 ± 0.06. Mean ± SD for OPMD and OSCC are 1.252 ± 0.06 and 1.91 ± 0.03, respectively, which showed a significant difference between OPMD and OSCC compared to healthy individuals.The complex changes of oral malignant transformation were closely linked to ghrelin via mTOR, PI3K, AKT and NF-κB signaling pathways, thus indicating that ghrelin could be a potentially useful target to regulate the malignant transformation of OPMD.