Potential for reversing miR-634-mediated cytoprotective processes to improve efficacy of chemotherapy against oral squamous cell carcinoma

Phuong Xuan Tran; Jun Inoue; Hiroyuki Harada; Johji Inazawa

doi:10.1016/j.omto.2022.02.002

Potential for reversing miR-634-mediated cytoprotective processes to improve efficacy of chemotherapy against oral squamous cell carcinoma

Mol Ther Oncolytics. 2022 Mar 8:24:897-908. doi: 10.1016/j.omto.2022.02.002. eCollection 2022 Mar 17.

Authors

Phuong Xuan Tran^{1

2}, Jun Inoue¹, Hiroyuki Harada², Johji Inazawa^{1

3}

Affiliations

¹ Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
² Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
³ Bioresource Research Center, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Abstract

For advanced oral squamous cell carcinoma (OSCC), increasing sensitivity to chemotherapy is a major challenge in improving treatment outcomes, and targeting cytoprotective processes that lead to the chemotherapy resistance of cancer cells may be therapeutically promising. Tumor-suppressive microRNAs (miRNAs) can target multiple cancer-promoting genes concurrently and are thus expected to be useful seeds for cancer therapeutics. We revealed that miR-634-mediated targeting of multiple cytoprotective process-related genes, including cellular inhibitor of apoptosis protein 1 (cIAP1), can effectively increase cisplatin (CDDP)-induced cytotoxicity and overcome CDDP resistance in OSCC cells. The combination of topical treatment with miR-634 ointment and administration of CDDP was synergistically effective against OSCC tumor growth in a xenograft mouse model. Furthermore, the expression of miR-634 target genes is frequently upregulated in primary OSCC tumors. Our study suggests that reversing miR-634-mediated cytoprotective processes activated in cancer cells is a potentially useful strategy to improve CDDP efficacy against advanced OSCC.

Keywords: OSCC; chemoresistance; cisplatin; miRNA therapeutics; topical treatment.