Oral cancer is the most heterogeneous cancer at clinical and histological levels. PI3K/AKT/mTOR pathway was identified as one of the most commonly modulated signals in oral cancer, which regulates major cellular and metabolic activity of the cell. Thus, various proteins of PI3K/AKT/mTOR pathway were used as therapeutic targets for oral cancer, to design more specific drugs with less off-target toxicity. This review sheds light on the regulation of PI3K/AKT/mTOR, and its role in controlling autophagy and associated apoptosis during the progression and metastasis of oral squamous type of malignancy (OSCC). In addition, we reviewed in detail the upstream activators and the downstream effectors of PI3K/AKT/mTOR signaling as potential therapeutic targets for oral cancer treatment.
Autophagy , Mouth Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Humans , Autophagy/physiology , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Apoptosis , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics
Oral premalignant disorders (OPMDs) are a group of potentially malignant conditions that pose a significant health burden globally. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as crucial regulators of gene expression and have been implicated in various biological processes, including carcinogenesis. This review synthesizes existing knowledge to provide a comprehensive understanding of the molecular mechanisms underlying OPMDs and to highlight the potential of miRNAs as promising biomarkers and therapeutic targets. Additionally, this review seeks to explore the potential of miRNA-based diagnostic biomarkers for early detection of OPMDs in the current literature on miRNAs in OPMDs, examining their involvement in disease pathogenesis, diagnostic potential, and therapeutic implications. Dysregulated miRNAs can target genes involved in critical cellular processes, such as cell cycle regulation, apoptosis, and DNA repair, leading to disease progression. Notably, miR-21, miR-31, miR-135b, and miR-486-5p have shown promise as potential biomarkers for early detection of oral premalignant lesions. Furthermore, the paper discusses the therapeutic implications of miRNAs in OPMDs. Preclinical studies have demonstrated the efficacy of miRNA-targeted therapies, such as miRNA mimics and inhibitors, in suppressing the growth of oral premalignant lesions. Early-phase clinical trials have shown promising results, indicating the potential for personalized treatment approaches. The findings underscore the importance of understanding the molecular mechanisms underlying these disorders and provide insights for the development of improved diagnostic and therapeutic strategies. However, they pose certain limitations given their intrinsic variability in expression profiles, the need for optimized isolation and detection methods, and potential hurdles in transitioning from preclinical success to clinical applications. Thus, future clinical studies are warranted to fully exploit the potential of miRNAs in the management of OPMDs.
Oral squamous cell carcinoma (OSCC) showed a seemingly increasing incidence in the last decade. In India, despite the use of tobacco decreased rapidly, in the past five years, the incidence pattern of OSCC over gender and age showed a drastic shift. About 51 % of the head and neck cancers are not associated with habits. Studies exploring various contributing factors in the incidence of this malignancy have documented. Recently, the epigenetic factors associated with the induction and progression of OSCC were explored. More than 90 % of the human genome is made up of non-coding transcriptome, which believed to be noises. However, these non-coding RNAs were identified to be the major epigenetic modulators, which raises concern over incidence of carcinoma in non-habit patients. H19 is a long non coding RNA which proved to be an effective biomarker in various carcinoma. Its role in oral squamous cell cancer was not investigated in depth. This review discusses in detail the various epigenetic role of H19 in inducing oral carcinogenesis.
Oral cancer is the most debilitating disease which affects the orderly life of a human. With so much advancement in research and technology, the average life expectancy of an individual with oral cancer appears to be about 5 years. The changing trend in incidence of oral cancer among young individuals and women without tobacco habits are ascending. Non habit related oral cancer are taking centre stage and multiple factors which induce complex biology are associated in such scenarios. To decipher the aetiology and to understand the process, these cancerous conditions are to be studied at molecular level. Saliva, the most non-invasively obtained body fluid are assessed for biomarkers exclusively in liquid biopsy. This fluid gives a huge platform to study number of molecules associated with oral cancer. Non coding RNAs are transcripts with no protein coding function. They are gaining more importance in recent times. Long noncoding RNA, microRNA are major types of noncoding transcriptome that influences in progression of oral cancer. They seem to play an important role in health and disease. Apart from these, circulating tumour cells, exosomes, extracellular vesicles, antigens and other proteins can be studied from saliva. This review is aimed to update the knowledge on current biomarkers in saliva associated with oral cancer and their epigenetic role in disease progression as well recent advances in detecting these markers to identify the stage of the disease, which will help in deciding the treatment protocol.
OBJECTIVE: To identify Helicobacter pylori (H. pylori) and related oncogenic and virulent proteins (CagA and VacA) in patients with gingivitis, periodontitis, oral cancer and gastric cancer. METHODS: Subgingival plaque samples were collected from 90 individuals with either gingivitis/periodontitis (group A, n = 30), oral cancer (group B, n = 30) and gastric cancer (group C, n = 30). H. pylori was identified by real-time polymerase chain reaction (RT-PCR). The virulent organisms were detected by identification of proteins CagA and VacA through Enzyme Linked Immuno-Sorbent Assay (ELISA). RESULTS: We identified the presence of H. pylori in subgingival plaque samples among a large majority (76/90) of our study cohort. The proportions of CagA and VacA identified among H. pylori individuals with periodontal inflammation and oral cancer were lower than those diagnosed with gastric cancer. Furthermore, the relative risk of oral cancer based on the presence of the organism was no different to those with gingivitis/periodontitis. CONCLUSION: The findings of our study do not indicate significant association between the organism and oral cancer, but preludes that the oral cavity could act as a potential niche for H. pylori. The possibility for CagA and VacA proteins to be pathogenic in oral cavity is highly possible and must be researched extensively.
Dental Plaque , Gingivitis , Helicobacter pylori , Mouth Neoplasms , Periodontitis , Stomach Neoplasms , Humans , Bacterial Proteins/genetics , Antigens, Bacterial/genetics , Cross-Sectional Studies , Oncogene Proteins , Genotype
Diabetes is one of the most significant health issues across the world. People identified with diabetes are more vulnerable to various infections and are at a greater risk of developing cardiovascular diseases. The plant-based food we consume often contains many sterol-based bioactive compounds. It is well documented that these compounds could effectively manage the processes of insulin metabolism and cholesterol regulation. Insulin resistance followed by hyperglycemia often results in oxidative stress level enhancement and increased reactive oxygen species production. At the molecular level, these changes induce apoptosis in pancreatic cells and hence lead to insulin insufficiency. Studies have proved that plant sterols can lower inflammatory and oxidative stress damage connected with DNA repair mechanisms. The effective forms of phyto compounds are polyphenols, terpenoids, and thiols abundant in vegetables, fruits, nuts, and seeds. The available conventional drug-based therapies for the prevention and management of diabetes are time-consuming, costly, and with life-threatening side effects. Thereby, the therapeutic management of diabetes with plant sterols available in our daily diet is highly welcome as there are no side effects. This review intends to offer an overview of the present scenario of the anti-diabetic compounds from food ingredients towards the therapeutic beneficial against diabetes.
It is of interest to document the inhibition of A2780 cell proliferation using Mollugo nudicaulis Lam.(M.nudicaulis) extract by MTT assay and by monitoring the CXCR4 and HER2 expression through RT-PCR analysis. Results shown that the n-hexane extract of M.nudicaulis have anticancer activity IC50 values of 32.46±0.92 µg/mL on A2780 cell lines. It is further found that the CXCR4 and HER2 mRNA and protein expression were significantly reduced in M.nudicaulis treated A2780 cell lines. Thus, the n-hexane extract of M.nudicaulis is a natural source of bioactive compounds as potential anticancer agents.
Oral Potentially Malignant Disorders such as leukoplakia, lichenplanus, Oral Submucous Fibrosis are most commonly encountered precancerous lesions in India. Although, usage of smoking tobacco has been decreased yet incidence of oral cancer seems to be in increasing trend. Apart from tobacco many non-tobacco causes are associated with the disease. Helicobacter pylori is a curved, flagellated bacterium that has been declared as group I carcinogen by WHO. They are proven causative agent for gastric carcinoma. They have been shown to harbour oral cavity by many authours. They produce onco-protein that causes DNA damage. CagA and VacA are such proteins that modulate certain oncogenes and tumour suppressor genes. In this study we have identified the organism from sub gingival plaque by PCR and those who harboured the organism were further subjected for identification of oncoproteins CagA and VacA by ELISA. This study shows that presence of organism in Oral leucoplakia, oral lichenplanus and Oral Submucous Fibrosis are statistically significant in comparison to control group (p>0.05). The presence of oncoproteins was also statistically significant in comparison to control group. These proteins are shown to accelerate inflammatory pathway thereby hasten the process of tumorigenesis. H.pylori infection as well the virulent strains can be diagnosed from oral cavity in the most non-invasive way at the earliest.
