• The Role Of Circular RNA in Oral Cancer
  • Maryam Rahmani,1,*
    1. Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran


  • Introduction: Circular RNAs (circRNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed con- tinuous loop and are highly represented in the eukaryotic transcriptome. CircRNAs are largely generated from exonic or intronic sequences, and reverse complementary sequences or RNA-binding proteins (RBPs) are neces- sary for circRNA biogenesis. The majority of circRNAs are conserved across species, are stable and resistant to RNase R, and often exhibit tissue/developmental-stage-specific expression. Emerging evidence indicates that circRNAs might play im- portant roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases. Oral Caner Five percent of all tumors occur in the head and neck, and approximately half of those occur specifically in the oral cavity. Of the 615,000 new cases of oral cavity tumors reported worldwide in 2000, 300,000 were primary oral cavity squamous cell carcinomas. Biomarkers are broadly classified as genomic, proteomic, or metabolomic. Molecular biology and oncology research studies on oral cancer biomarkers focus on identifying key biological molecules or markers that could be linked to cancer development, risk assessment, screening, recurrence prediction, indicating prognosis, indicating invasion/metastasis and monitoring therapeutic responses of cancer. Cluster of differentiation factor 34 is a salivary biomarker that can identify recurrence potential of oral squamous cell carcinoma (OSCC). Integrin α3 and integrin β4 are genomic biomarkers that are helpful in estimating the risk of regional and hematogenous dissemination of malignant oral squamous cells. Oral cancer is a major public health problem, and there is an increasing trend for oral cancer to affect young men and women. Public awareness is poor, and many patients present with late-stage disease, contributing to high mortality. Oral cancer is often preceded by a clinical premalignant phase accessible to visual inspection, and thus there are opportunities for earlier detection and to reduce morbidity and mortality. Screening asymptomatic individuals by systematic visual oral examinations to detect the disease has been shown to be feasible. A positive screen includes both oral cancer and oral potentially malignant disorders. Risk Of oral Cancer Inhalation of secondhand smoke (SHS) causes several diseases, including lung cancer. In conclusion, the most important risk factor for developing oral cancer is tobacco consumption followed by alcohol consumption Circular RNA Function CircRNAs are covalently closed, circular RNA molecules that typically comprise exonic sequences and are spliced at canonical splice sites. This feature of gene expression was first recognized in humans and mouse, but it quickly emerged that it was common across essentially all eukaryotes studied by molecular biologists. CircRNA abundance, and even which alternatively spliced circRNA isoforms are expressed, varies by cell type and can exceed the abundance of the traditional linear mRNA or ncRNA transcript. CircRNAs are enriched in the brain and increase in abundance during fetal development.
  • Methods: Accumulating evidence has demonstrated that circular RNAs (circRNAs) play important roles in regulating gene expression involved in tumor development. Importantly, the expression levels of circATRNL1 decreased after irradiation treatment, and upregulation of circATRNL1 enhanced the radiosensitivity of OSCC through suppressing proliferation and the colony survival fraction, inducing apoptosis and cell-cycle arrest. Moreover, we observed that circATRNL1 could directly bind to microRNA-23a-3p (miR-23a-3p) and relieve inhibition for the target gene PTEN Circular RNAs (circRNAs) consist of covalently closed structures without a free 3′ poly(A) tail or 5′ cap. Due to their loop structures, circRNAs are largely stable and resistant to RNA degradation by endonucleases. Therefore, they have much longer circulatory half-lives compared with linear RNAs, such as microRNA and long non-coding RNA. CircRNAs have multiple microRNA binding sites, and circRNA binding leads to regulation of the expression of those miRNAs and their target genes by acting as a competing endogenous RNA. However, the underlying molecular mechanisms and clinical correlation between circRNAs and tumor progression are not well understood. In the present study, we identified circRNA-102450 as a novel tumor suppressor and potential biomarker of regional lymph node metastasis from OSCC using liquid biopsy-based droplet digital PCR, a highly sensitive method for absolute quantification.Circular RNAs (circRNAs), which act as initial factors and promoters in different diseases, are noncoding RNAs (ncRNAs) in eukaryotes. Accumulating studies have proven that dysregulation of circRNAs is relevant to the occurrence and development of multiple cancers. circHIPK3, as a member of circRNA, is frequently expressed in many diseases, such as diabetes, age-related cataract, idiopathic pulmonary fibrosis, preeclampsia, osteoblasts and retinal vascular dysfunction, leading to disease development and progression.
  • Results: The most common type of oral cancer is squamous cell carcinoma, which accounts for ap- proximately 9 out of 10 malignancies. Therefore, the oral cancer problem primarily concerns the diagnosis, biology, and manage- ment of squamous cell carcinoma. It discusses the current understanding of circRNA functions, the emerging roles of circRNA in cancer. Circular RNAs (circRNAs) are a class of single-stranded closed RNA molecules that undergo a specific backsplicing from pre-mRNA. Some functionally characterized circRNAs have critical roles in gene regulation through various actions, including sponging microRNAs and proteins as well as regulating transcription and splicing. Moreover, most circRNAs are aberrantly expressed in different cancer types, and some of them have been reported to play important roles in the development and progression of cancer.
  • Conclusion: Oral cancer is the sixth most common cancer worldwide and accounts for over a half a million new patients diagnosed each year. The incidence of oral carcinoma has significant geographic variation.. Circular RNAs (circRNAs) are a class of single-stranded closed RNA molecules that are formed by precursor mRNA back-splicing or skipping events of thousands of genes in eukaryotes as covalently closed continuous loops. High-throughput sequencing and bioinformatics approaches have uncovered the broad expression of circRNAs across species. Their high stability, abundance, and evolutionary conservation among species points to their distinct properties and diverse cellular functions as efficient microRNAs and protein sponges; they also play important roles in modulating transcription and splicing. Additionally, most circRNAs are aberrantly expressed in pathological conditions and in a tissue-specific manner such as development and progression of cancer. highlight the characteristics, functions, and mechanisms of action of circRNAs in cancer; provide an overview of recent progress in the circRNA field and future application of circRNAs as cancer biomarkers and novel therapeutic targets.
  • Keywords: Circular RNA,Oral Cancer,Biomarker