MicroRNAs as valuable biomarkers in early diagnosis, prognosis, and targeted therapy of oral cavity cancer

MicroRNAs as valuable biomarkers in early diagnosis, prognosis, and targeted therapy of oral cavity cancer Oral cancer (OC) is the most prevalent type of head and neck cancer that manifests in the tongue, lips, and floor of the mouth. Smoking, alcohol drinking, and human papillomavirus (HPV) infection are known as the main risk factors. Current therapeutic approaches such as chemotherapy, radiotherapy, and combination radio/chemo therapy are applied for oral cavity cancer patients; however, overall survival (OS) and disease-free survival (DFS) remain at a low rate (۵۰-۶۰%). The miRNAs are small RNA molecules with ۱۸-۲۵ nt in length that regulate gene expression by interacting with the target mRNA's ۳-untranslated region (۳UTR) post-transcriptionally. Although ۳UTR binding induces inhibition or degradation of the target gene, rarely interactions with ۵UTR, promoter, and coding region have also been reported that may induce gene expression. The miRNA expression can be evaluated in tissues and body bio-fluids like blood, saliva, serum, plasma, urine, etc. Many of the miRNAs are discovered to be associated with OC diagnosis or prognosis, and some are suggested as biomarkers. The miRNA down-regulates a gene that plays an oncogenic role, known as tumor suppressor-miR, which involves the cell cycle process and apoptosis. Whenever a miRNA binds to a tumor suppressor gene and down-regulates it, we named it onco-miR which improves tumor cell growth, invasion, metastasis, and angiogenesis. Simultaneous suppression of oncomiRs and replacement of tumor suppressor miRNAs, applying tumor suppressor miRs, or repressing oncomiRs by antagomirs are practical approaches in designing an OC treatment strategy. OncomiRs like miR-۲۱, miR-۱۵۵, miR-۱۹۶, miR-۱۲۳۷, miR-۳۱, miR-۴۵۵, miR-۱۸۱, miR-۱۸۴, miR-۱۳۴, miR-۱۴۶, miR-۹۳, miR-۳۷۲, miR-۳۷۳, miR-۱۰۳a-۳p, miR-۴۵۴, miR-۶۵۴-۵p, miR-۱۸۸-۵p, miR-۶۲۶, miR-۴۵۱۳, miR-۹۴۴, and miR-۶۵۰ are discovered that up-regulate in OC cell lines and patient. On the other hand, some miRNAs play a role like tumor suppressors and are detected to be downregulated in OC cell lines and patients, including miR-۲۰۴, miR۱۲۵b, miR-۹, miR-۲۶a/b, miR-۴۹۱-۵p, miR-۳۷۵, miR-۳۲۰, miR-۲۱۸, miR-۲۰۵, miR-۱۸۱a, miR-۱۳۸, miR-۱۲۴, miR-۹۹a, miR-۳۴, miR-۲۹a, miR-۱۷, etc. Although the miRNAs regulate the expression of oncogenes and tumor suppressors to modulate OC progression, some challenges in therapeutic approaches remain unsolved. First, one miRNA can bind to multiple genes, and on the other hand, one gene can be regulated by multiple miRNAs. For this reason, selecting one or more than one miRNA for clinical application of the oral cavity and lip cancers must be considered meticulously and accurately. Second, miRNAs are small and naked molecules sensitive to nuclease digestion in cellular environments. In this way, scientists have extensively suggested miR-target therapy using nanoparticle delivery systems and exosomes. However, a definitive protocol for this aim has not been reported. Third, although miRNAs have critical roles in the tumorigenesis process, there is no definitive protocol for applying them. Although clinical trials showed promising outcomes for applying miRNAs for early diagnosis, prognosis, and therapy, more extensive studies are needed to solve the challenges. Keywords: miRNA, Biomarkers, Oral cancer, target therapy.

کلیدواژه ها:

miRNA ، Biomarkers ، Oral cancer ، target therapy