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This review evaluates the biological roles and salivary diagnostic potential of microRNA-21 (miR-21) and miR-31, two miRNAs repeatedly associated with OSCC pathogenesis and progression. We examine current clinical evidence supporting their use as salivary biomarkers and discuss major sources of methodological variability, including differences in saliva collection, RNA recovery, normalization, and diagnostic thresholds. We pay particular attention to the transition from laboratory-based RT-qPCR to Recombinase Polymerase Amplification (RPA) for decentralized detection. Although RPA offers rapid, low-temperature amplification with reduced hardware requirements, mature miRNAs present a key technical challenge because their short length requires prior target extension or conversion. Successful chairside translation will depend on standardized sample processing, robust target-specific amplification, contamination control, and validation in clinically relevant early-stage and comparator populations.<\/jats:p>","DOI":"10.3390\/cells15191799","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:43:24Z","timestamp":1790880204000},"page":"1799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Salivary miR-21 and miR-31 in Oral Squamous Cell Carcinoma: Molecular Pathogenesis, Diagnostic Significance, and Translation to Isothermal RPA"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4935-7312","authenticated-orcid":false,"given":"Jyotsna S.","family":"Ranbhise","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2232-0350","authenticated-orcid":false,"given":"Manish Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeong Rok","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-7668","authenticated-orcid":false,"given":"Sung Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7117-1008","authenticated-orcid":false,"given":"Insug","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ghanem, A.S., Memon, H.A., and Nagy, A.C. 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