Chemotherapeutic Drug Resistance Associated with Differential miRNA Expression of miR-375 and miR-27 among Oral Cancer Cell Lines

Abstract

Recent advances have suggested that non-coding miRNAs (such as miR-21, miR-27, miR-145, miR-155, miR-365, miR-375 and miR-494) may be involved in multiple aspects of oral cancer chemotherapeutic responsiveness. This study evaluated whether these specific miRNAs are correlated with oral cancer responsiveness to chemotherapies, including Paclitaxel, Cisplatin and Fluorouracil (5FU). Commercially available and well-characterized oral squamous cell carcinoma cell lines (SCC4, SCC9, SCC15, SCC25 and CAL27) revealed differing resistance and chemosensitivity to these agents—with SCC9 and SCC25 demonstrating the most resistance to all chemotherapeutic agents. SCC9 and SCC25 were also the only cell lines that expressed miR-375, and were the only cell lines that did not express miR-27. In addition, the expression of miR-375 was associated with the upregulation of Rearranged L-myc fusion (RLF) and the downregulation of Centriolar protein B (POC1), whereas lack of miR-27 expression was associated with Nucleophosmin 1 (NPM1) expression. These data have revealed important regulatory pathways and mechanisms associated with oral cancer proliferation and resistance that must be explored in future studies of potential therapeutic interventions.

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

“…The primary objective of this current study was to provide an evaluation of the specific microRNA expression profile of the oral cancer cell line SCC15 lacking chemotherapeutic resistance, which may provide new potential insights into potential treatments and therapies. These results confirmed the upregulation of miR-145 among this chemosensitive cell line previously reported by this group [47]. This supports other research that demonstrates that the downregulation of miR-145 expression was associated with oral cancer diagnosis and progression, while miR-145 upregulation correlated with improved prognosis and increased survival [31,39].…”

“…Recent work from this group has demonstrated the upregulation of miR-21 and miR-365 among oral cancers, as well as the confirmation of the downregulation of miR-27 among chemoresistant oral cancer cell lines [46,47]. Moreover, this most recent study found that the upregulation of miR-145 and the downregulation of miR-155 were also strongly correlated with a lack of chemotherapy resistance, although the mechanism(s) responsible for this observation remained unidentified [47].…”

“…First, this study employed wellcharacterized, commercially available cell lines of oral cancers to create a model system for analyzing and evaluating chemoresistance and chemosensitivity, which may not reflect the diversity or range of expression profiles among current patients with oral cancer. However, this type of in vitro validation system has been used in multiple research studies that sought to analyze and evaluate types of cancer-related chemotherapy resistance and sensitivity, as well as the mechanisms that may be operational in these systems [47,71,73]. Although this type of research is essential to uncover chemoresistance and chemosensitivity and the underlying mechanisms that may be responsible, these results must be analyzed and validated in future studies that utilize primary tissue samples from oral cancer patients and a wider range of tumor explants [74,75].…”

“…Recent work from this group has demonstrated the upregulation of miR-21 and miR-365 among oral cancers, as well as the confirmation of the downregulation of miR-27 among chemoresistant oral cancer cell lines [46,47]. Moreover, this most recent study found that the upregulation of miR-145 and the downregulation of miR-155 were also strongly correlated with a lack of chemotherapy resistance, although the mechanism(s) responsible for this observation remained unidentified [47]. The goal of this current study was to provide an evaluation of these microRNAs and their downstream targets to create a more comprehensive understanding of their potential role in the lack of chemotherapeutic resistance among oral cancers, which could provide new potential treatments and therapies [45,47,48].…”

“…Moreover, this most recent study found that the upregulation of miR-145 and the downregulation of miR-155 were also strongly correlated with a lack of chemotherapy resistance, although the mechanism(s) responsible for this observation remained unidentified [47]. The goal of this current study was to provide an evaluation of these microRNAs and their downstream targets to create a more comprehensive understanding of their potential role in the lack of chemotherapeutic resistance among oral cancers, which could provide new potential treatments and therapies [45,47,48]. This study employed a prospective research design to evaluate commercially available oral cancer cell lines for the lack of chemotherapy resistance and then to subsequently screen for the associated upregulation or downregulation of microRNAs, as well as their most likely validated downstream targets using quantitative polymerase chain reaction (qPCR).…”