Differential Expression of MicroRNA MiR-145 and MiR-155 Downstream Targets in Oral Cancers Exhibiting Limited Chemotherapy Resistance

Background: New evidence has suggested that non-coding microRNAs play a significant role in mediating and modulating chemotherapy resistance, particularly among oral cancers. One recent study found that the expression of miR-145 and lack of miR-155 expression strongly correlated with a limited chemotherapy resistance to Cisplatin, 5-Fluorouracil and Paclitaxel , although the mechanism(s) responsible for these observations remain unidentified. Methods: Using commercially available cell lines of oral squamous cell carcinoma (OSCC), RNA was isolated using phenol:chloroform extraction. The isolated RNA was converted into cDNA by reverse transcription and subsequently screened for the presence or absence of downstream targets of miR-145 and miR-155 using qPCR. Results: The expression of miR-145 downstream gene targets (n=13) were analyzed in all OSCC cells. The expression pattern of three miR-145 gene targets could be correlated to the degree of chemotherapy resistance. In the least chemotherapy resistant cells (SCC15), altered expression of KCN and SRGAP2 and the absence of FAM135A expression were observed. This differential expression was unique to the SCC15 cells and not detected in any of the other OSCC cell lines. Conclusions: These data strongly support that differential regulation of these three downstream targets is related to the chemotoxic sensitivity of the SCC15 oral cancer cell line. The potential involvement of these targets must be further investigated to determine how and whether mechanisms of these cellular pathways may be involved in the observed lack of chemotherapy resistance. These data may be important to design targets or treatments to reduce chemotherapy resistance and improve patient treatment outcomes.