A higher expression level of miR in Tongue
A higher expression level of miR-21 in Tongue Squamous Cell Carcinoma (TSCC) is correlated with advanced clinical stage, poor differentiation and lymph node metastasis suggesting its potential to be used as a prognostic marker for TSCC patient survival . MiR-31, miR-17, miR-125b, miR-155, miR-181, miR-205, and miR-let7d were also found to be associated with lymph node metastasis and poor patient survival [39,, , , , , ] and thus, could be used to detect the metastatic potential of cancer. Since a single miRNA targets multiple mRNAs, cancer prognosis and risk of metastasis might be correlated with both the miRNAs and their target mRNAs that are enriched in a particular tissue type. Cells enriched with oncogenic mRNAs would result in decreased tumor progression due to miRNA mediated post transcriptional repression of their target oncogenic mRNAs, while Dexmedetomidine abundantly expressing tumor suppressor mRNAs would result in accelerated progression by miRNA mediated repression of their target tumor suppressor mRNAs. The expressions of target mRNAs also depend on the tissue types, clinical stages of the cancer, environmental risk factors and habits of the patients.
Therapeutic role of circulating miRNAs in oral cancer The ability to manipulate miRNA expression and function by local and systemic delivery of miRNA inhibitors or miRNA mimics has recently gained immense interest as a novel therapeutic approach [68,69]. The advantage of miRNA based cancer therapy lies in the ability of miRNAs to concurrently target multiple effectors of pathways involved in cell proliferation, differentiation, and survival. However, the major challenges are in vivo delivery of these polyanionic oligonucleotides. Naked miRNAs cannot pass through hydrophobic cell membranes and are also prone to be degraded by RNase. Chemically modified miRNA-targeting antisense oligonucleotides and nanoparticle based delivery approaches have shown considerable promise in improving both bioavailability and stability of miRNAs. However, efficient targeting to specific areas of the body still remains challenging . Resistance to chemotherapy radiotherapy are major challenges in the management of OSCC patients. Recent studies have linked resistance to chemo- and radiotherapy in OSCC to altered miRNA expression (Fig. 1). MiR-375, a tumor suppressor miRNA, is reported to be lower than normal in the plasma of OSCC patients [25,71]. It has been shown that the miR-375 inhibits growth and enhances radiosensitivity of OSCC by targeting IGF1R . A decreased expression of miR-375 might be associated with resistance to radiotherapy and hence, overexpressing miR-375 by miRNA mimics might result in increased sensitivity and responsiveness to radiotherapy in OSCC patients. Another tumor suppressor, miRNA Let-7d, is found to be lower in the serum of OSCC patients . Reduced expression of this miRNA showed increase in chemoresistance in OSCC patients . Hence, targeted delivery of Let-7d mimics is expected to result in increased chemosensitivity and responsiveness of patients towards chemotherapy. A decreased expression of miR-200b is reported to be associated with chemotherapeutic resistance and poor prognosis of TSCC patients , whereas overexpression of miR-196a is associated with resistance to radiotherapy in HNSCC . MiR-21 is an oncogenic miRNA that is associated with chemosensitivity of several human cancer cell lines to anticancer agents. For example, miR-21 modulates chemosensitivity of TSCC cells to cisplatin by targeting PDCD4 , while inhibition of miR-21 by anti-miRs or siRNA is reported to induce sensitivity of TSCC cells to cisplatin . In a study by Shiiba et al., transfection of OSCC cell lines with miR-125b resulted in a decreased proliferation rate and enhanced radiosensitivity . Hence, in-vivo delivery of this miRNA might result in enhanced response to treatment. Reduced expression of miR-100, miR-130a and miR-197 and an elevated expression of miR-181b, miR-181d, miR-101 and miR-195 are also reported to be correlated with multiple drug resistance in HNSCC . Despite the promising therapeutic roles of miRNAs in cancer, further studies and elaborate research are required for the development of an effective in-vivo delivery system for optimal uptake and targeted delivery of miRNAs.